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4. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, Zychlinsky, A, Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, and Zychlinsky, A

Abstract

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Published
2019

5. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Cossarizza, A. (Andrea), Chang, H.-D. (Hyun-Dong), Radbruch, A. (Andreas), Andrä, I. (Immanuel), Annunziato, F. (Francesco), Bacher, P. (Petra), Barnaba, V. (Vincenzo), Battistini, L. (Luca), Bauer, W.M. (Wolfgang M.), Baumgart, S. (Sabine), Becher, B. (Burkhard), Beisker, W. (Wolfgang), Berek, C. (Claudia), Blanco, A. (Alfonso), Borsellino, G. (Giovanna), Boulais, P.E. (Philip E.), Brinkman, R.R. (Ryan R.), Büscher, M. (Martin), Busch, D.H. (Dirk), Bushnell, T.P. (Timothy P.), Cao, X. (Xuetao), Cavani, A. (Andrea), Chattopadhyay, P.K. (Pratip K.), Cheng, Q. (Qingyu), Chow, S. (Sue), Clerici, M. (Mario), Cooke, A. (Anne), Cosma, A. (Antonio), Cosmi, L. (Lorenzo), Cumano, A. (Ana), Dang, V.D. (Van Duc), Davies, D. (Derek), De Biasi, S. (Sara), Del Zotto, G. (Genny), Della Bella, S. (Silvia), Dellabona, P. (Paolo), Deniz, G. (Gunnur), Dessing, M. (Mark), Diefenbach, A. (Andreas), Santo, J.P. (James) di, Dieli, F. (Francesco), Dolf, A. (Andreas), Donnenberg, V.S. (Vera S.), Dörner, A. (Andrea), Ehrhardt, G.R.A. (Götz R. A.), Endl, E. (Elmar), Engel, P. (Pablo), Engelhardt, B. (Britta), Esser, C. (Charlotte), Everts, B. (Bart), Falk, C.S. (Christine S.), Fehniger, T.A. (Todd A.), Filby, A. (Andrew), Fillatreau, S. (Simon), Follo, M. (Marie), Förster, I. (Irmgard), Foster, J. (John), Foulds, G.A. (Gemma A.), Frenette, P.S. (Paul S.), Galbraith, D. (David), Garbi, N. (Natalio), García-Godoy, M.D. (Maria Dolores), Ghoreschi, K. (Kamran), Gibellini, L. (Lara), Goettlinger, C. (Christoph), Goodyear, C.S. (Carl), Gori, A. (Andrea), Grogan, J.L. (Jane), Gross, M. (Mor), Grützkau, A. (Andreas), Grummitt, D. (Daryl), Hahn, J. (Jonas), Hammer, Q. (Quirin), Hauser, A.E. (Anja E.), Haviland, D.L. (David L.), Hedley, D. (David), Herrera, G. (Guadalupe), Herrmann, M. (Martin), Hiepe, F. (Falk), Holland, T. (Tristan), Hombrink, P. (Pleun), Houston, J.P. (Jessica P.), Hoyer, B.F. (Bimba F.), Huang, B. (Bo), Hunter, C.A. (Christopher A.), Iannone, A. (Anna), Jäck, H.-M. (Hans-Martin), Jávega, B. (Beatriz), Jonjic, S. (Stipan), Juelke, K. (Kerstin), Jung, S. (Steffen), Kaiser, T. (Toralf), Kalina, T. (Tomas), Keller, B. (Baerbel), Khan, S. (Srijit), Kienhöfer, D. (Deborah), Kroneis, T. (Thomas), Kunkel, D. (Désirée), Kurts, C. (Christian), Kvistborg, P. (Pia), Lannigan, J. (Joanne), Lantz, O. (Olivier), Larbi, A. (Anis), LeibundGut-Landmann, S. (Salome), Leipold, M.D. (Michael D.), Levings, M.K., Litwin, V. (Virginia), Liu, Y. (Yanling), Lohoff, M. (Michael), Lombardi, G. (Giovanna), Lopez, L. (Lilly), Lovett-Racke, A. (Amy), Lubberts, E.W. (Erik), Ludewig, B. (Burkhard), Lugli, E. (Enrico), Maecker, H.T. (Holden T.), Martrus, G. (Glòria), Matarese, G. (Giuseppe), Maueröder, C. (Christian), McGrath, M. (Mairi), McInnes, I.B. (Iain), Mei, H.E. (Henrik E.), Melchers, F. (Fritz), Melzer, S. (Susanne), Mielenz, D. (Dirk), Mills, K. (Kingston), Mjösberg, J.M. (Jenny), Moore, J. (Jonni), Moran, B. (Barry), Moretta, A. (Alessandro), Moretta, L. (Lorenzo), Mosmann, T.R. (Tim R.), Müller, S. (Susann), Müller, W. (Werner), Münz, C. (Christian), Multhoff, G. (Gabriele), Munoz, L.E. (Luis Enrique), Murphy, K.M. (Kenneth M.), Nakayama, T. (Toshinori), Nasi, M. (Milena), Neudörfl, C. (Christine), Nolan, J. (John), Nourshargh, S. (Sussan), O'Connor, J.-E. (José-Enrique), Ouyang, W. (Wenjun), Oxenius, A. (Annette), Palankar, R. (Raghav), Panse, I. (Isabel), Peterson, P. (Pärt), Peth, C. (Christian), Petriz, J. (Jordi), Philips, D. (Daisy), Pickl, W. (Winfried), Piconese, S. (Silvia), Pinti, M. (Marcello), Pockley, A.G. (A. Graham), Podolska, M.J. (Malgorzata Justyna), Pucillo, C. (Carlo), Quataert, S.A. (Sally A.), Radstake, T.R.D.J. (Timothy R. D. J.), Rajwa, B. (Bartek), Rebhahn, J.A. (Jonathan A.), Recktenwald, D. (Diether), Remmerswaal, D. (Daniëlle), Rezvani, K. (Katy), Rico, L.G. (Laura G.), Robinson, J.P. (J. Paul), Romagnani, C. (Chiara), Rubartelli, A. (Anna), Ruland, J. (Jürgen), Sakaguchi, S. (Shimon), Sala-de-Oyanguren, F. (Francisco), Samstag, Y. (Yvonne), Sanderson, S. (Sharon), Sawitzki, B. (Birgit), Scheffold, A. (Alexander), Schiemann, M. (Matthias), Schildberg, F. (Frank), Schimisky, E. (Esther), Schmid, S.A. (Stephan A), Schmitt, S. (Steffen), Schober, K. (Kilian), Schüler, T. (Thomas), Schulz, A.R. (Axel Ronald), Schumacher, T.N. (Ton), Scotta, C. (Cristiano), Shankey, T.V. (T. Vincent), Shemer, A. (Anat), Simon, A.-K. (Anna-Katharina), Spidlen, J. (Josef), Stall, A.M. (Alan M.), Stark, R. (Regina), Stehle, C. (Christina), Stein, M. (Merle), Steinmetz, T. (Tobit), Stockinger, H. (Hannes), Takahama, Y. (Yousuke), Tarnok, A. (Attila), Tian, Z. (ZhiGang), Toldi, G. (Gergely), Tornack, J. (Julia), Traggiai, E. (Elisabetta), Trotter, J. (Joe), Ulrich, H. (Henning), van der Braber, M. (Marlous), Van Lier, R.A.W. (Rene A. W.), Veldhoen, M. (Marcello), Vento-Asturias, S. (Salvador), Vieira, P. (Paulo), Voehringer, D. (David), Volk, H.D. (Hans), von Volkmann, K. (Konrad), Waisman, A. (Ari), Walker, R. (Rachael), Ward, M.D. (Michael D.), Warnatz, K. (Klaus), Warth, S. (Sarah), Watson, J.V. (James V.), Watzl, C. (Carsten), Wegener, L. (Leonie), Wiedemann, A. (Annika), Wienands, J. (Jürgen), Willimsky, G. (Gerald), Wing, J. (James), Wurst, P. (Peter), Yu, L. (Liping), Yue, A. (Alice), Zhang, Q. (Qianjun), Zhao, Y. (Yi), Ziegler, S. (Susanne), Zimmermann, J. (Jakob), Cossarizza, A. (Andrea), Chang, H.-D. (Hyun-Dong), Radbruch, A. (Andreas), Andrä, I. (Immanuel), Annunziato, F. (Francesco), Bacher, P. (Petra), Barnaba, V. (Vincenzo), Battistini, L. (Luca), Bauer, W.M. (Wolfgang M.), Baumgart, S. (Sabine), Becher, B. (Burkhard), Beisker, W. (Wolfgang), Berek, C. (Claudia), Blanco, A. (Alfonso), Borsellino, G. (Giovanna), Boulais, P.E. (Philip E.), Brinkman, R.R. (Ryan R.), Büscher, M. (Martin), Busch, D.H. (Dirk), Bushnell, T.P. (Timothy P.), Cao, X. (Xuetao), Cavani, A. (Andrea), Chattopadhyay, P.K. (Pratip K.), Cheng, Q. (Qingyu), Chow, S. (Sue), Clerici, M. (Mario), Cooke, A. (Anne), Cosma, A. (Antonio), Cosmi, L. (Lorenzo), Cumano, A. (Ana), Dang, V.D. (Van Duc), Davies, D. (Derek), De Biasi, S. (Sara), Del Zotto, G. (Genny), Della Bella, S. (Silvia), Dellabona, P. (Paolo), Deniz, G. (Gunnur), Dessing, M. (Mark), Diefenbach, A. (Andreas), Santo, J.P. (James) di, Dieli, F. (Francesco), Dolf, A. (Andreas), Donnenberg, V.S. (Vera S.), Dörner, A. (Andrea), Ehrhardt, G.R.A. (Götz R. A.), Endl, E. (Elmar), Engel, P. (Pablo), Engelhardt, B. (Britta), Esser, C. (Charlotte), Everts, B. (Bart), Falk, C.S. (Christine S.), Fehniger, T.A. (Todd A.), Filby, A. (Andrew), Fillatreau, S. (Simon), Follo, M. (Marie), Förster, I. (Irmgard), Foster, J. (John), Foulds, G.A. (Gemma A.), Frenette, P.S. (Paul S.), Galbraith, D. (David), Garbi, N. (Natalio), García-Godoy, M.D. (Maria Dolores), Ghoreschi, K. (Kamran), Gibellini, L. (Lara), Goettlinger, C. (Christoph), Goodyear, C.S. (Carl), Gori, A. (Andrea), Grogan, J.L. (Jane), Gross, M. (Mor), Grützkau, A. (Andreas), Grummitt, D. (Daryl), Hahn, J. (Jonas), Hammer, Q. (Quirin), Hauser, A.E. (Anja E.), Haviland, D.L. (David L.), Hedley, D. (David), Herrera, G. (Guadalupe), Herrmann, M. (Martin), Hiepe, F. (Falk), Holland, T. (Tristan), Hombrink, P. (Pleun), Houston, J.P. (Jessica P.), Hoyer, B.F. (Bimba F.), Huang, B. (Bo), Hunter, C.A. (Christopher A.), Iannone, A. (Anna), Jäck, H.-M. (Hans-Martin), Jávega, B. (Beatriz), Jonjic, S. (Stipan), Juelke, K. (Kerstin), Jung, S. (Steffen), Kaiser, T. (Toralf), Kalina, T. (Tomas), Keller, B. (Baerbel), Khan, S. (Srijit), Kienhöfer, D. (Deborah), Kroneis, T. (Thomas), Kunkel, D. (Désirée), Kurts, C. (Christian), Kvistborg, P. (Pia), Lannigan, J. (Joanne), Lantz, O. (Olivier), Larbi, A. (Anis), LeibundGut-Landmann, S. (Salome), Leipold, M.D. (Michael D.), Levings, M.K., Litwin, V. (Virginia), Liu, Y. (Yanling), Lohoff, M. (Michael), Lombardi, G. (Giovanna), Lopez, L. (Lilly), Lovett-Racke, A. (Amy), Lubberts, E.W. (Erik), Ludewig, B. (Burkhard), Lugli, E. (Enrico), Maecker, H.T. (Holden T.), Martrus, G. (Glòria), Matarese, G. (Giuseppe), Maueröder, C. (Christian), McGrath, M. (Mairi), McInnes, I.B. (Iain), Mei, H.E. (Henrik E.), Melchers, F. (Fritz), Melzer, S. (Susanne), Mielenz, D. (Dirk), Mills, K. (Kingston), Mjösberg, J.M. (Jenny), Moore, J. (Jonni), Moran, B. (Barry), Moretta, A. (Alessandro), Moretta, L. (Lorenzo), Mosmann, T.R. (Tim R.), Müller, S. (Susann), Müller, W. (Werner), Münz, C. (Christian), Multhoff, G. (Gabriele), Munoz, L.E. (Luis Enrique), Murphy, K.M. (Kenneth M.), Nakayama, T. (Toshinori), Nasi, M. (Milena), Neudörfl, C. (Christine), Nolan, J. (John), Nourshargh, S. (Sussan), O'Connor, J.-E. (José-Enrique), Ouyang, W. (Wenjun), Oxenius, A. (Annette), Palankar, R. (Raghav), Panse, I. (Isabel), Peterson, P. (Pärt), Peth, C. (Christian), Petriz, J. (Jordi), Philips, D. (Daisy), Pickl, W. (Winfried), Piconese, S. (Silvia), Pinti, M. (Marcello), Pockley, A.G. (A. Graham), Podolska, M.J. (Malgorzata Justyna), Pucillo, C. (Carlo), Quataert, S.A. (Sally A.), Radstake, T.R.D.J. (Timothy R. D. J.), Rajwa, B. (Bartek), Rebhahn, J.A. (Jonathan A.), Recktenwald, D. (Diether), Remmerswaal, D. (Daniëlle), Rezvani, K. (Katy), Rico, L.G. (Laura G.), Robinson, J.P. (J. Paul), Romagnani, C. (Chiara), Rubartelli, A. (Anna), Ruland, J. (Jürgen), Sakaguchi, S. (Shimon), Sala-de-Oyanguren, F. (Francisco), Samstag, Y. (Yvonne), Sanderson, S. (Sharon), Sawitzki, B. (Birgit), Scheffold, A. (Alexander), Schiemann, M. (Matthias), Schildberg, F. (Frank), Schimisky, E. (Esther), Schmid, S.A. (Stephan A), Schmitt, S. (Steffen), Schober, K. (Kilian), Schüler, T. (Thomas), Schulz, A.R. (Axel Ronald), Schumacher, T.N. (Ton), Scotta, C. (Cristiano), Shankey, T.V. (T. Vincent), Shemer, A. (Anat), Simon, A.-K. (Anna-Katharina), Spidlen, J. (Josef), Stall, A.M. (Alan M.), Stark, R. (Regina), Stehle, C. (Christina), Stein, M. (Merle), Steinmetz, T. (Tobit), Stockinger, H. (Hannes), Takahama, Y. (Yousuke), Tarnok, A. (Attila), Tian, Z. (ZhiGang), Toldi, G. (Gergely), Tornack, J. (Julia), Traggiai, E. (Elisabetta), Trotter, J. (Joe), Ulrich, H. (Henning), van der Braber, M. (Marlous), Van Lier, R.A.W. (Rene A. W.), Veldhoen, M. (Marcello), Vento-Asturias, S. (Salvador), Vieira, P. (Paulo), Voehringer, D. (David), Volk, H.D. (Hans), von Volkmann, K. (Konrad), Waisman, A. (Ari), Walker, R. (Rachael), Ward, M.D. (Michael D.), Warnatz, K. (Klaus), Warth, S. (Sarah), Watson, J.V. (James V.), Watzl, C. (Carsten), Wegener, L. (Leonie), Wiedemann, A. (Annika), Wienands, J. (Jürgen), Willimsky, G. (Gerald), Wing, J. (James), Wurst, P. (Peter), Yu, L. (Liping), Yue, A. (Alice), Zhang, Q. (Qianjun), Zhao, Y. (Yi), Ziegler, S. (Susanne), and Zimmermann, J. (Jakob)

Published
2017
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6. Hypervariable Region 1 Variants Act as TCR Antagonists for Hepatitis C Virus-Specific CD4+ T Cells

Author

LOREDANA FRASCA, Del Porto, P., Tuosto, L., Marinari, B., Scotta, C., Carbonari, M., Nicosia, A., and Piccolella, E.

Subjects
CD4-Positive T-Lymphocytes, Antigen Presentation, Binding Sites, Molecular Sequence Data, Immunology, Receptors, Antigen, T-Cell, Antigen-Presenting Cells, Down-Regulation, Epitopes, T-Lymphocyte, HLA-DR Antigens, Hepacivirus, Cell Line, Clone Cells, Mice, Amino Acid Substitution, Animals, Cytokines, Humans, Immunology and Allergy, Amino Acid Sequence, Peptides, Antigens, Viral
Abstract

In various human viral infections, the appearance of mutated epitopes displaying TCR antagonistic activity has been correlated with the severity and persistence of infection. In hepatitis C virus (HCV) infection, where the virus persistence has been associated with the rapid and substantial Ag modifications occurring during replication, TCR antagonism has been evidenced in CD8+ T cell responses. However, CD4+ T cell antagonism may be another important strategy by which HCV eludes a protective response, because sustained Th responses directed against several HCV Ags are associated with a self-limited course of infection. The data reported here represent the first evidence that variants of the hypervariable region (HVR1) of the putative Envelope 2 protein of HCV can act as powerful TCR antagonists for HVR1-specific CD4+ T cells isolated from HCV-infected individuals. Using classical antagonism assays, we observed strong inhibition of cellular proliferation and cytokine production when the agonist and the antagonist ligands were simultaneously presented by the same APCs. The presence in HVR1 of conserved residues, critical for binding to HLA-DR molecules, supports the function of HVR1 variants as TCR antagonists. In conclusion, our data evidence an antagonism phenomenon, which was achieved by naturally occurring class II-restricted T cell epitopes whose mechanism was addressed in terms of the antagonist capacity to inhibit agonist-mediated TCR down-regulation and early signal transduction.

Published
1999

8. Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells

Author

Scotta, C., primary, Fanelli, G., additional, Hoong, S. J., additional, Romano, M., additional, Lamperti, E. N., additional, Sukthankar, M., additional, Guggino, G., additional, Fazekasova, H., additional, Ratnasothy, K., additional, Becker, P. D., additional, Afzali, B., additional, Lechler, R. I., additional, and Lombardi, G., additional

Published
2015
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13. Differential effects of rapamycin and retinoic acid on expansion, stability and suppressive qualities of human CD4+CD25+FOXP3+ T regulatory cell subpopulations

Author

Scotta, C., primary, Esposito, M., additional, Fazekasova, H., additional, Fanelli, G., additional, Edozie, F. C., additional, Ali, N., additional, Xiao, F., additional, Peakman, M., additional, Afzali, B., additional, Sagoo, P., additional, Lechler, R. I., additional, and Lombardi, G., additional

Published
2012
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14. OC-066 Gut specific regulatory t cells – a new frontier for crohn’s disease therapy

Author

Goldberg, R, Scotta, C, Cooper, D, Irving, P, Sanderson, J, Shpigel, N, Marelli-Berg, F, Lombardi, G, and Lord, G

Abstract

IntroductionWe have recently shown that Tregs isolated from the peripheral blood of patients with Crohn’s Disease (CD) can be expanded in vitrofor therapeutic purposes. This is a critical step to developing cell based therapy for Crohn’s disease. The immune system used retinoic acid (ATRA) to induce a4b7 and thus prime Tregs to home to the gut. We sought use ATRA in-vitroin order to engineer gut specific Tregs for our Phase 1 trial in Crohn’s Disease. We then validated our findings in-vitroand in-vivo.MethodTregs were isolated from peripheral blood of CD patients. ATRA supplementation was tested in standard culture conditions. The expression of a4b7 was assessed by flow cytometry. Suppression assays were performed using autologous effector T cells (Teff). An ibidi flow chamber system coated with recombinant human MAdCAM-1 was used for in-vitrotrafficking experiments. SCID mice xenografted with foetal intestinal small bowel were used for in-vivoexperiments.ResultsEx-vivoexpansion of Tregs in the presence of ATRA significantly induced the expression of a4b7 compared to Rapamycin alone (5.57%±3.12 vs 82.8%±9.5, p=0.0057) Cells treated with Rapa+ATRA maintained their superior suppressive ability compared to Rapamycin treated Tregs (95.8%±3.5% vs 91.15%±10.1% p=ns; at Treg:Teff 1:1 ratio). RAPA+ATRA Tregs did not produce IFNy or IL17 under pro-inflammatory cytokine challenge. When flowed through a MAdCAm-1 coated chamber, significantly higher numbers of Rapa+ATRA treated cells were observed to roll (Rapa 0.83±0.40 vs Rapa+ATRA 10.17±2.54 p=0.005), crawl (Rapa 0 vs Rapa+ATRA 4±0.89 p=0.001) and firmly adhere (Rapa 0.33±0.21 vs Rapa+ATRA 36.8±1.78, p<0.001) than those treated with Rapa alone. When Tregs were transferred into mice, a higher proportion of Tregs were found in xenografts of animals treated with Rapa+ATRA Tregs compared Rapa Tregs (12.10 (7.54–22.83) vs 4.97 (1.72–7.63), p=0.0056). Importantly there was a higher proportion of Tregs in inflamed xenografts of animals treated with Rapa+ATRA Tregs compared to those treated with Rapa Tregs (18.35 (12.95–28.63) vs 6.78 (2.65–9.61),p=0.0095).ConclusionThe addition of ATRA to Treg culture in-vitroconfers a gut homing phenotype. This is functionally relevant in-vitroand in-vivo. The treatment maintains the highly suppressive and phenotypically stable phenotype of these cells. These gut specific Tregs will be implemented in our first in man trial Treg therapy for Crohn’s disease.Disclosure of InterestNone Declared

Published
2017
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15. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Lara Gibellini, Sussan Nourshargh, Susanna Cardell, Wlodzimierz Maslinski, Mar Felipo-Benavent, Florian Mair, Hans-Martin Jäck, Lilly Lopez, Klaus Warnatz, John Trowsdale, Diana Ordonez, Marcus Eich, William Hwang, Anne Cooke, Dirk Mielenz, Alberto Orfao, Winfried F. Pickl, Vladimir Benes, Alice Yue, T. Vincent Shankey, Maria Tsoumakidou, Virginia Litwin, Gelo Victoriano Dela Cruz, Andrea Cavani, Sara De Biasi, Larissa Nogueira Almeida, Jonathan J M Landry, Claudia Haftmann, Charlotte Esser, Ana Cumano, Anneke Wilharm, Francesco Dieli, Rudi Beyaert, Alessio Mazzoni, Burkhard Ludewig, Carlo Pucillo, Dirk H. Busch, Joe Trotter, Stipan Jonjić, Marc Veldhoen, Josef Spidlen, Aja M. Rieger, Dieter Adam, Srijit Khan, Todd A. Fehniger, Giuseppe Matarese, Maximilien Evrard, Christian Maueröder, Steffen Schmitt, Kristin A. Hogquist, Barry Moran, Raghavendra Palankar, Markus Feuerer, S Schmid, Susann Rahmig, Amy E. Lovett-Racke, James V. Watson, Megan K. Levings, Susanne Melzer, Dinko Pavlinic, Christopher M. Harpur, Christina Stehle, A. Graham Pockley, Toshinori Nakayama, Attila Tárnok, Juhao Yang, Michael Lohoff, Paulo Vieira, Francisco Sala-de-Oyanguren, Christian Kurts, Anastasia Gangaev, Alfonso Blanco, Hans Scherer, Regine J. Dress, Bruno Silva-Santos, Kiyoshi Takeda, Bimba F. Hoyer, Ilenia Cammarata, Daryl Grummitt, Isabel Panse, Günnur Deniz, Bianka Baying, Friederike Ebner, Esther Schimisky, Leo Hansmann, Thomas Kamradt, Edwin van der Pol, Daniel Scott-Algara, Anna Iannone, Giorgia Alvisi, Sebastian R. Schulz, Francesco Liotta, Irmgard Förster, Beatriz Jávega, Hans-Peter Rahn, Caetano Reis e Sousa, Livius Penter, Xuetao Cao, David P. Sester, Keisuke Goda, Peter Wurst, Iain B. McInnes, Ricardo T. Gazzinelli, Federica Piancone, Gerald Willimsky, Yotam Raz, Pärt Peterson, Wolfgang Fritzsche, Yvonne Samstag, Martin Büscher, Thomas Schüler, Susanne Hartmann, Robert J. Wilkinson, Anna E. S. Brooks, Steven L. C. Ketelaars, Catherine Sautès-Fridman, Anna Rubartelli, Petra Bacher, Katja Kobow, Marco A. Cassatella, Andrea Hauser, Henrik E. Mei, Kilian Schober, Silvia Della Bella, Graham Anderson, Michael D. Ward, Garth Cameron, Sebastian Lunemann, Katharina Kriegsmann, Katarzyna M. Sitnik, Brice Gaudilliere, Chantip Dang-Heine, Marcello Pinti, Paul Klenerman, Frank A. Schildberg, Joana Barros-Martins, Laura G. Rico, Hanlin Zhang, Christian Münz, Thomas Dörner, Jakob Zimmermann, Andrea M. Cooper, Jonni S. Moore, Andreas Diefenbach, Yanling Liu, Wolfgang Bauer, Tobit Steinmetz, Katharina Pracht, Leonard Tan, Peter K. Jani, Alan M. Stall, Petra Hoffmann, Christine S. Falk, Jasmin Knopf, Simon Fillatreau, Hans-Dieter Volk, Luis E. Muñoz, David L. Haviland, William W. Agace, Jonathan Rebhahn, Ljiljana Cvetkovic, Mohamed Trebak, Jordi Petriz, Mario Clerici, Diether J. Recktenwald, Anders Ståhlberg, Tristan Holland, Helen M. McGuire, Sa A. Wang, Christian Kukat, Thomas Kroneis, Laura Cook, Wan Ting Kong, Xin M. Wang, Britta Engelhardt, Pierre Coulie, Genny Del Zotto, Sally A. Quataert, Kata Filkor, Gabriele Multhoff, Bartek Rajwa, Federica Calzetti, Hans Minderman, Cosima T. Baldari, Jens Geginat, Hervé Luche, Gert Van Isterdael, Linda Schadt, Sophia Urbanczyk, Giovanna Borsellino, Liping Yu, Dale I. Godfrey, Achille Anselmo, Rachael C. Walker, Andreas Grützkau, David W. Hedley, Birgit Sawitzki, Silvia Piconese, Maria Yazdanbakhsh, Burkhard Becher, Ramon Bellmas Sanz, Michael Delacher, Hyun-Dong Chang, Immanuel Andrä, Hans-Gustaf Ljunggren, José-Enrique O'Connor, Ahad Khalilnezhad, Sharon Sanderson, Federico Colombo, Götz R. A. Ehrhardt, Inga Sandrock, Enrico Lugli, Christian Bogdan, James B. Wing, Susann Müller, Tomohiro Kurosaki, Derek Davies, Ester B. M. Remmerswaal, Kylie M. Quinn, Christopher A. Hunter, Andreas Radbruch, Timothy P. Bushnell, Anna Erdei, Sabine Adam-Klages, Pascale Eede, Van Duc Dang, Rieke Winkelmann, Thomas Korn, Gemma A. Foulds, Dirk Baumjohann, Matthias Schiemann, Manfred Kopf, Jan Kisielow, Lisa Richter, Jochen Huehn, Gloria Martrus, Alexander Scheffold, Jessica G. Borger, Sidonia B G Eckle, John Bellamy Foster, Anna Katharina Simon, Alicia Wong, Mübeccel Akdis, Gisa Tiegs, Toralf Kaiser, James McCluskey, Anna Vittoria Mattioli, Aaron J. Marshall, Hui-Fern Koay, Eva Orlowski-Oliver, Anja E. Hauser, J. Paul Robinson, Jay K. Kolls, Luca Battistini, Mairi McGrath, Jane L. Grogan, Natalio Garbi, Timothy Tree, Kingston H. G. Mills, Stefan H. E. Kaufmann, Wolfgang Schuh, Ryan R. Brinkman, Tim R. Mosmann, Vincenzo Barnaba, Andreas Dolf, Lorenzo Cosmi, Bo Huang, Andreia C. Lino, Baerbel Keller, René A. W. van Lier, Alexandra J. Corbett, Paul S. Frenette, Pleun Hombrink, Helena Radbruch, Sofie Van Gassen, Olivier Lantz, Lorenzo Moretta, Désirée Kunkel, Kirsten A. Ward-Hartstonge, Armin Saalmüller, Leslie Y. T. Leung, Salvador Vento-Asturias, Paola Lanuti, Alicia Martínez-Romero, Sarah Warth, Zhiyong Poon, Diana Dudziak, Andrea Cossarizza, Kovit Pattanapanyasat, Konrad von Volkmann, Jessica P. Houston, Agnès Lehuen, Andrew Filby, Pratip K. Chattopadhyay, Stefano Casola, Annika Wiedemann, Hannes Stockinger, Jürgen Ruland, Arturo Zychlinsky, Claudia Waskow, Katrin Neumann, Ari Waisman, Lucienne Chatenoud, Sudipto Bari, Kamran Ghoreschi, David W. Galbraith, Yvan Saeys, Hamida Hammad, Andrea Gori, Miguel López-Botet, Gabriel Núñez, Sabine Ivison, Michael Hundemer, Dorothea Reimer, Mark C. Dessing, Günter J. Hämmerling, Rudolf A. Manz, Tomas Kalina, Jonas Hahn, Holden T. Maecker, Hendy Kristyanto, Martin S. Davey, Henning Ulrich, Michael L. Dustin, Takashi Saito, Yousuke Takahama, Milena Nasi, Johanna Huber, Jürgen Wienands, Paolo Dellabona, Andreas Schlitzer, Michael D. Leipold, Kerstin H. Mair, Christian Peth, Immo Prinz, Chiara Romagnani, José M. González-Navajas, Josephine Schlosser, Marina Saresella, Matthias Edinger, Dirk Brenner, Nicole Baumgarth, Rikard Holmdahl, Fang-Ping Huang, Guadalupe Herrera, Malte Paulsen, Gergely Toldi, Luka Cicin-Sain, Reiner Schulte, Christina E. Zielinski, Thomas Winkler, Christoph Goettlinger, Philip E. Boulais, Jennie H M Yang, Antonio Celada, Heike Kunze-Schumacher, Julia Tornack, Florian Ingelfinger, Jenny Mjösberg, Andy Riddell, Leonie Wegener, Thomas Höfer, Christoph Hess, James P. Di Santo, Anna E. Oja, J. Kühne, Willem van de Veen, Mary Bebawy, Alberto Mantovani, Bart Everts, Giovanna Lombardi, Laura Maggi, Anouk von Borstel, Pia Kvistborg, Elisabetta Traggiai, A Ochel, Nima Aghaeepour, Charles-Antoine Dutertre, Matthieu Allez, Thomas Höllt, Wenjun Ouyang, Regina Stark, Maries van den Broek, Shimon Sakaguchi, Paul K. Wallace, Silvano Sozzani, Francesca LaRosa, Annette Oxenius, Malgorzata J. Podolska, Ivana Marventano, Wilhelm Gerner, Oliver F. Wirz, Britta Frehse, Gevitha Ravichandran, Martin Herrmann, Carl S. Goodyear, Gary Warnes, Helen Ferry, Stefan Frischbutter, Tim R. Radstake, Salomé LeibundGut-Landmann, Yi Zhao, Axel Schulz, Angela Santoni, Pablo Engel, Daniela C. Hernández, Andreas Acs, Cristiano Scottà, Francesco Annunziato, Thomas Weisenburger, Wolfgang Beisker, Sue Chow, Fritz Melchers, Daniel E. Speiser, Immanuel Kwok, Florent Ginhoux, Dominic A. Boardman, Natalie Stanley, Carsten Watzl, Marie Follo, Erik Lubberts, Andreas Krueger, Susanne Ziegler, Göran K. Hansson, David Voehringer, Antonia Niedobitek, Eleni Christakou, Lai Guan Ng, Sabine Baumgart, Nicholas A Gherardin, Antonio Cosma, Orla Maguire, Jolene Bradford, Daniel Schraivogel, Linda Quatrini, Stephen D. Miller, Rheumatology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Institute of Clinical Molecular Biology, Kiel University, Department of Life Sciences [Siena, Italy], Università degli Studi di Siena = University of Siena (UNISI), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Dulbecco Telethon Institute/Department of Biology, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, European Molecular Biology Laboratory [Heidelberg] (EMBL), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Fondazione Santa Lucia (IRCCS), Department of Immunology, Chinese Academy of Medical Sciences, FIRC Institute of Molecular Oncology Foundation, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, Monash University [Clayton], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biopharmacy [Bruxelles, Belgium] (Institute for Medical Immunology IMI), Université libre de Bruxelles (ULB), Charité Hospital, Humboldt-Universität zu Berlin, Agency for science, technology and research [Singapore] (A*STAR), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], Kennedy Institute of Rheumatology [Oxford, UK], Imperial College London, Theodor Kocher Institute, University of Bern, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] ( IUF), Université Lumière - Lyon 2 (UL2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Edinburgh, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Universitat de Barcelona (UB), Rheumatologie, Cell Biology, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Delft University of Technology (TU Delft), Medical Inflammation Research, Karolinska Institutet [Stockholm], Department of Photonics Engineering [Lyngby], Technical University of Denmark [Lyngby] (DTU), Dpt of Experimental Immunology [Braunschweig], Helmholtz Centre for Infection Research (HZI), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Histology and Embryology, University of Rijeka, Freiburg University Medical Center, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Institute of Integrative Biology, Molecular Biomedicine, Berlin Institute of Health (BIH), Laboratory for Lymphocyte Differentiation, RIKEN Research Center, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Surgery [Vancouver, BC, Canada] (Child and Family Research Institute), University of British Columbia (UBC)-Child and Family Research Institute [Vancouver, BC, Canada], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, King‘s College London, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brustzentrum Kantonsspital St. Gallen, Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Heinrich Pette Institute [Hamburg], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Immunology and Cell Biology, Mario Negri Institute, Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation, Institute of Translational Medicine, Klinik für Dermatologie, Venerologie und Allergologie, School of Biochemistry and Immunology, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Centre de Recherche Publique- Santé, Université du Luxembourg (Uni.lu), William Harvey Research Institute, Barts and the London Medical School, University of Michigan [Ann Arbor], University of Michigan System, Centro de Investigacion del Cancer (CSIC), Universitario de Salamanca, Molecular Pathology [Tartu, Estonia], University of Tartu, Hannover Medical School [Hannover] (MHH), Centre d'Immunologie de Marseille - Luminy (CIML), Monash Biomedicine Discovery Institute, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Data Mining and Modelling for Biomedicine [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, RIKEN Research Center for Allergy and Immunology, Osaka University [Osaka], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institute of Medical Immunology [Berlin, Germany], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Otto-von-Guericke University [Magdeburg] (OVGU), SUPA School of Physics and Astronomy [University of St Andrews], University of St Andrews [Scotland]-Scottish Universities Physics Alliance (SUPA), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), General Pathology and Immunology (GPI), University of Brescia, Université de Lausanne (UNIL), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Dept. Pediatric Cardiology, Universität Leipzig [Leipzig], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Cardiovascular Sciences, Albany Medical College, Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), Department of Information Technology [Gent], Universiteit Gent, Department of Plant Systems Biology, Department of Plant Biotechnology and Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Division of Molecular Immunology, Institute for Immunology, Department of Geological Sciences, University of Oregon [Eugene], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Colorado [Colorado Springs] (UCCS), FACS laboratory, Cancer Research, London, Cancer Research UK, Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Barbara Davis Center for Childhood Diabetes (BDC), University of Colorado Anschutz [Aurora], School of Computer and Electronic Information [Guangxi University], Guangxi University [Nanning], School of Materials Science and Engineering, Nanyang Technological University [Singapour], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Work in the laboratory of Dieter Adam is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 125440785 – SFB 877, Project B2.Petra Hoffmann, Andrea Hauser, and Matthias Edinger thank BD Biosciences®, San José, CA, USA, and SKAN AG, Bale, Switzerland for fruitful cooperation during the development, construction, and installation of the GMP‐compliant cell sorting equipment and the Bavarian Immune Therapy Network (BayImmuNet) for financial support.Edwin van der Pol and Paola Lanuti acknowledge Aleksandra Gąsecka M.D. for excellent experimental support and Dr. Rienk Nieuwland for textual suggestions. This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO‐TTW), research program VENI 15924.Jessica G Borger, Kylie M Quinn, Mairi McGrath, and Regina Stark thank Francesco Siracusa and Patrick Maschmeyer for providing data.Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14‐1. Rudolf A. Manz was supported by the Excellence Cluster 'Inflammation at Interfaces' (EXC 306/2).Susanne Hartmann and Friederike Ebner were supported by the German Research Foundation (GRK 2046).Hans Minderman was supported by NIH R50CA211108.This work was funded by the Deutsche Forschungsgemeinschaft through the grant TRR130 (project P11 and C03) to Thomas H. Winkler.Ramon Bellmàs Sanz, Jenny Kühne, and Christine S. Falk thank Jana Keil and Kerstin Daemen for excellent technical support. The work was funded by the Germany Research Foundation CRC738/B3 (CSF).The work by the Mei laboratory was supported by German Research Foundation Grant ME 3644/5‐1 and TRR130 TP24, the German Rheumatism Research Centre Berlin, European Union Innovative Medicines Initiative ‐ Joint Undertaking ‐ RTCure Grant Agreement 777357, the Else Kröner‐Fresenius‐Foundation, German Federal Ministry of Education and Research e:Med sysINFLAME Program Grant 01ZX1306B and KMU‐innovativ 'InnoCyt', and the Leibniz Science Campus for Chronic Inflammation (http://www.chronische-entzuendung.org).Axel Ronald Schulz, Antonio Cosma, Sabine Baumgart, Brice Gaudilliere, Helen M. McGuire, and Henrik E. Mei thank Michael D. Leipold for critically reading the manuscript.Christian Kukat acknowledges support from the ISAC SRL Emerging Leaders program.John Trowsdale received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement 695551)., European Project: 7728036(1978), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Università degli Studi di Milano = University of Milan (UNIMI), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universität Heidelberg [Heidelberg] = Heidelberg University, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Oxford-NIHR Biomedical Research Centre, Universität Bonn = University of Bonn, Università degli Studi di Firenze = University of Florence (UniFI), Università degli studi di Genova = University of Genoa (UniGe), Universidad de Salamanca, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Université de Lausanne = University of Lausanne (UNIL), Universität Leipzig, Universiteit Gent = Ghent University (UGENT), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Cossarizza, A., Chang, H. -D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W., Aghaeepour, N., Akdis, M., Allez, M., Almeida, L. N., Alvisi, G., Anderson, G., Andra, I., Annunziato, F., Anselmo, A., Bacher, P., Baldari, C. T., Bari, S., Barnaba, V., Barros-Martins, J., Battistini, L., Bauer, W., Baumgart, S., Baumgarth, N., Baumjohann, D., Baying, B., Bebawy, M., Becher, B., Beisker, W., Benes, V., Beyaert, R., Blanco, A., Boardman, D. A., Bogdan, C., Borger, J. G., Borsellino, G., Boulais, P. E., Bradford, J. A., Brenner, D., Brinkman, R. R., Brooks, A. E. S., Busch, D. H., Buscher, M., Bushnell, T. P., Calzetti, F., Cameron, G., Cammarata, I., Cao, X., Cardell, S. L., Casola, S., Cassatella, M. A., Cavani, A., Celada, A., Chatenoud, L., Chattopadhyay, P. K., Chow, S., Christakou, E., Cicin-Sain, L., Clerici, M., Colombo, F. S., Cook, L., Cooke, A., Cooper, A. M., Corbett, A. J., Cosma, A., Cosmi, L., Coulie, P. G., Cumano, A., Cvetkovic, L., Dang, V. D., Dang-Heine, C., Davey, M. S., Davies, D., De Biasi, S., Del Zotto, G., Dela Cruz, G. V., Delacher, M., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Di Santo, J. P., Diefenbach, A., Dieli, F., Dolf, A., Dorner, T., Dress, R. J., Dudziak, D., Dustin, M., Dutertre, C. -A., Ebner, F., Eckle, S. B. G., Edinger, M., Eede, P., Ehrhardt, G. R. A., Eich, M., Engel, P., Engelhardt, B., Erdei, A., Esser, C., Everts, B., Evrard, M., Falk, C. S., Fehniger, T. A., Felipo-Benavent, M., Ferry, H., Feuerer, M., Filby, A., Filkor, K., Fillatreau, S., Follo, M., Forster, I., Foster, J., Foulds, G. A., Frehse, B., Frenette, P. S., Frischbutter, S., Fritzsche, W., Galbraith, D. W., Gangaev, A., Garbi, N., Gaudilliere, B., Gazzinelli, R. T., Geginat, J., Gerner, W., Gherardin, N. A., Ghoreschi, K., Gibellini, L., Ginhoux, F., Goda, K., Godfrey, D. I., Goettlinger, C., Gonzalez-Navajas, J. M., Goodyear, C. S., Gori, A., Grogan, J. L., Grummitt, D., Grutzkau, A., Haftmann, C., Hahn, J., Hammad, H., Hammerling, G., Hansmann, L., Hansson, G., Harpur, C. M., Hartmann, S., Hauser, A., Hauser, A. E., Haviland, D. L., Hedley, D., Hernandez, D. C., Herrera, G., Herrmann, M., Hess, C., Hofer, T., Hoffmann, P., Hogquist, K., Holland, T., Hollt, T., Holmdahl, R., Hombrink, P., Houston, J. P., Hoyer, B. F., Huang, B., Huang, F. -P., Huber, J. E., Huehn, J., Hundemer, M., Hunter, C. A., Hwang, W. Y. K., Iannone, A., Ingelfinger, F., Ivison, S. M., Jack, H. -M., Jani, P. K., Javega, B., Jonjic, S., Kaiser, T., Kalina, T., Kamradt, T., Kaufmann, S. H. E., Keller, B., Ketelaars, S. L. C., Khalilnezhad, A., Khan, S., Kisielow, J., Klenerman, P., Knopf, J., Koay, H. -F., Kobow, K., Kolls, J. K., Kong, W. T., Kopf, M., Korn, T., Kriegsmann, K., Kristyanto, H., Kroneis, T., Krueger, A., Kuhne, J., Kukat, C., Kunkel, D., Kunze-Schumacher, H., Kurosaki, T., Kurts, C., Kvistborg, P., Kwok, I., Landry, J., Lantz, O., Lanuti, P., Larosa, F., Lehuen, A., LeibundGut-Landmann, S., Leipold, M. D., Leung, L. Y. T., Levings, M. K., Lino, A. C., Liotta, F., Litwin, V., Liu, Y., Ljunggren, H. -G., Lohoff, M., Lombardi, G., Lopez, L., Lopez-Botet, M., Lovett-Racke, A. E., Lubberts, E., Luche, H., Ludewig, B., Lugli, E., Lunemann, S., Maecker, H. T., Maggi, L., Maguire, O., Mair, F., Mair, K. H., Mantovani, A., Manz, R. A., Marshall, A. J., Martinez-Romero, A., Martrus, G., Marventano, I., Maslinski, W., Matarese, G., Mattioli, A. V., Maueroder, C., Mazzoni, A., Mccluskey, J., Mcgrath, M., Mcguire, H. M., Mcinnes, I. B., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Miller, S. D., Mills, K. H. G., Minderman, H., Mjosberg, J., Moore, J., Moran, B., Moretta, L., Mosmann, T. R., Muller, S., Multhoff, G., Munoz, L. E., Munz, C., Nakayama, T., Nasi, M., Neumann, K., Ng, L. G., Niedobitek, A., Nourshargh, S., Nunez, G., O'Connor, J. -E., Ochel, A., Oja, A., Ordonez, D., Orfao, A., Orlowski-Oliver, E., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Pattanapanyasat, K., Paulsen, M., Pavlinic, D., Penter, L., Peterson, P., Peth, C., Petriz, J., Piancone, F., Pickl, W. F., Piconese, S., Pinti, M., Pockley, A. G., Podolska, M. J., Poon, Z., Pracht, K., Prinz, I., Pucillo, C. E. M., Quataert, S. A., Quatrini, L., Quinn, K. M., Radbruch, H., Radstake, T. R. D. J., Rahmig, S., Rahn, H. -P., Rajwa, B., Ravichandran, G., Raz, Y., Rebhahn, J. A., Recktenwald, D., Reimer, D., Reis e Sousa, C., Remmerswaal, E. B. M., Richter, L., Rico, L. G., Riddell, A., Rieger, A. M., Robinson, J. P., Romagnani, C., Rubartelli, A., Ruland, J., Saalmuller, A., Saeys, Y., Saito, T., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sandrock, I., Santoni, A., Sanz, R. B., Saresella, M., Sautes-Fridman, C., Sawitzki, B., Schadt, L., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schimisky, E., Schlitzer, A., Schlosser, J., Schmid, S., Schmitt, S., Schober, K., Schraivogel, D., Schuh, W., Schuler, T., Schulte, R., Schulz, A. R., Schulz, S. R., Scotta, C., Scott-Algara, D., Sester, D. P., Shankey, T. V., Silva-Santos, B., Simon, A. K., Sitnik, K. M., Sozzani, S., Speiser, D. E., Spidlen, J., Stahlberg, A., Stall, A. M., Stanley, N., Stark, R., Stehle, C., Steinmetz, T., Stockinger, H., Takahama, Y., Takeda, K., Tan, L., Tarnok, A., Tiegs, G., Toldi, G., Tornack, J., Traggiai, E., Trebak, M., Tree, T. I. M., Trotter, J., Trowsdale, J., Tsoumakidou, M., Ulrich, H., Urbanczyk, S., van de Veen, W., van den Broek, M., van der Pol, E., Van Gassen, S., Van Isterdael, G., van Lier, R. A. W., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H. -D., von Borstel, A., von Volkmann, K., Waisman, A., Walker, R. V., Wallace, P. K., Wang, S. A., Wang, X. M., Ward, M. D., Ward-Hartstonge, K. A., Warnatz, K., Warnes, G., Warth, S., Waskow, C., Watson, J. V., Watzl, C., Wegener, L., Weisenburger, T., Wiedemann, A., Wienands, J., Wilharm, A., Wilkinson, R. J., Willimsky, G., Wing, J. B., Winkelmann, R., Winkler, T. H., Wirz, O. F., Wong, A., Wurst, P., Yang, J. H. M., Yang, J., Yazdanbakhsh, M., Yu, L., Yue, A., Zhang, H., Zhao, Y., Ziegler, S. M., Zielinski, C., Zimmermann, J., Zychlinsky, A., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, Netherlands Organization for Scientific Research, German Research Foundation, European Commission, European Research Council, Repositório da Universidade de Lisboa, CCA - Imaging and biomarkers, Experimental Immunology, AII - Infectious diseases, AII - Inflammatory diseases, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, and Landsteiner Laboratory

Subjects
0301 basic medicine, Consensus, Immunology, Consensu, Cell Separation, Biology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Guidelines, Allergy and Immunology, medicine, Cell separation, Immunology and Allergy, Humans, guidelines, flow cytometry, immunology, medicine.diagnostic_test, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Cell sorting, Flow Cytometry, Cell selection, Data science, 3. Good health, 030104 developmental biology, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, 030215 immunology, Human
Abstract

All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).

Published
2019

16. Regulatory cell therapy in kidney transplantation (The ONE Study):a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials

Author

Kathryn J. Wood, Birgit Sawitzki, James A. Hutchinson, Leslie Brent, Cristiano Scottà, Christoph Meyenberg, P Friend, Kerry Crisalli, Manuela Battaglia, Natalie M Otto, Ben James, Eva C. Guinan, M. C. Cuturi, Alexander Scheffold, William Petchey, Ulrich Kunzendorf, William J. Burlingham, Fadi Issa, Antonio Secchi, Petra Reinke, Giovanna Lombardi, James F. Markmann, Hans-Dieter Volk, David Game, Matthias Edinger, Norbert Ahrens, Ian S.D. Roberts, Michael Kapinsky, Maria P. Hernandez-Fuentes, Bernhard Banas, Sandra Karitzky, Nathalie Dupas, Carsten A. Böger, Edward K. Geissler, Tewfik Miloud, Stephan Schlickeiser, Paul N. Harden, Qizhi Tang, Gilles Blancho, Tobias Bergler, Karsten Juerchott, Robert I. Lechler, Hans J. Schlitt, Josep M. Grinyó, Laura Contreras-Ruiz, Rossana Caldara, Joanna Hester, Mathias Streitz, A. Bushell, Rachel Hilton, Régis Josien, Stuart J. Knechtle, Robert Öllinger, Laurence A. Turka, Cécile Braudeau, Aurélie Moreau, Peter J. Morris, Jeffrey A. Bluestone, Sang-Mo Kang, Ingrid Mutzbauer, Jeroen B. van der Net, Sawitzki, B., Harden, P. N., Reinke, P., Moreau, A., Hutchinson, J. A., Game, D. S., Tang, Q., Guinan, E. C., Battaglia, M., Burlingham, W. J., Roberts, I. S. D., Streitz, M., Josien, R., Boger, C. A., Scotta, C., Markmann, J. F., Hester, J. L., Juerchott, K., Braudeau, C., James, B., Contreras-Ruiz, L., van der Net, J. B., Bergler, T., Caldara, R., Petchey, W., Edinger, M., Dupas, N., Kapinsky, M., Mutzbauer, I., Otto, N. M., Ollinger, R., Hernandez-Fuentes, M. P., Issa, F., Ahrens, N., Meyenberg, C., Karitzky, S., Kunzendorf, U., Knechtle, S. J., Grinyo, J., Morris, P. J., Brent, L., Bushell, A., Turka, L. A., Bluestone, J. A., Lechler, R. I., Schlitt, H. J., Cuturi, M. C., Schlickeiser, S., Friend, P. J., Miloud, T., Scheffold, A., Secchi, A., Crisalli, K., Kang, S. -M., Hilton, R., Banas, B., Blancho, G., Volk, H. -D., Lombardi, G., Wood, K. J., Geissler, E. K., and Publica

Subjects
Graft Rejection, medicine.medical_specialty, Kidney Disease, Basiliximab, medicine.medical_treatment, T-Lymphocytes, Clinical Trials and Supportive Activities, Cell- and Tissue-Based Therapy, Renal and urogenital, 030204 cardiovascular system & hematology, T-Lymphocytes, Regulatory, Medical and Health Sciences, Organ transplantation, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Clinical Research, Internal medicine, General & Internal Medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, Kidney transplantation, Immunosuppression Therapy, Transplantation, business.industry, Macrophages, Immunosuppression, General Medicine, Dendritic Cells, Organ Transplantation, medicine.disease, Kidney Transplantation, Regulatory, Patient Safety, business, Immunosuppressive Agents, medicine.drug
Abstract

Background:Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. Methods:The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered withClinicalTrials.gov,NCT01656135,NCT02252055,NCT02085629,NCT02244801,NCT02371434,NCT02129881, andNCT02091232. Findings:The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2–18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. Interpretation:Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression.

Published
2020

17. Antibody-selected mimics of hepatitis C virus hypervariable region 1 activate both primary and memory Th lymphocytes

Author

Paola Del Porto, Enza Piccolella, Loredana Frasca, Luigi Racioppi, Cristiano Scottà, Ilaria Versace, Caterina Pasquazzi, Alfredo Nicosia, Anna Maria Masci, L., Frasca, C., Scotta, P. D., Porto, Nicosia, Alfredo, C., Pasquazzi, I., Versace, A. M., Masci, Racioppi, Luigi, E., Piccolella, Frasca, L, Scotta, C, DEL PORTO, P, Nicosia, A, Pasquazzi, C, Versace, I, Masci, Am, and Piccolella, E.

Subjects
Adult, Male, T-Lymphocytes, viruses, Hepatitis C virus, Receptors, Antigen, T-Cell, VACCINE, Hepacivirus, Cross Reactions, VARIANTS, Biology, Lymphocyte Activation, medicine.disease_cause, CHIMPANZEES, CELL RECOGNITION, Epitope, Cell Line, Epitopes, Immune system, medicine, Humans, Lymphocytes, SPECIFICITY, Aged, ENVELOPE, B-Lymphocytes, Mutation, Hepatology, Immunogenicity, Molecular Mimicry, HLA-DR, T-cell receptor, virus diseases, PEPTIDES, T-Lymphocytes, Helper-Inducer, Hepatitis C, Chronic, Middle Aged, Complementarity Determining Regions, Virology, MIMOTOPES, digestive system diseases, Hypervariable region, Immunology, biology.protein, Female, MONOCLONAL-ANTIBODIES, Antibody, Immunologic Memory
Abstract

An ideal strategy that leads to a vaccine aimed at controlling viral escape may be that of preventing the replication of escape mutants by eliciting a T- and B-cell repertoire directed against many viral variants. The hypervariable region 1 (HVR1) of the putative envelope 2 protein that presents B and T epitopes shown to induce protective immunity against hepatitis C virus (HCV), might be suitable for this purpose if its immunogenicity can be improved by generating mimics that induce broad, highly cross-reactive, anti-HVR1 responses. Recently we described a successful approach to select HVR1 mimics (mimotopes) incorporating the variability found in a great number of viral variants. In this report we explore whether these mimotopes, designed to mimic B-cell epitopes, also mimic helper T-cell epitopes. The first interesting observation is that mimotopes selected for their reactivity to HVR1-specific antibodies of infected patients also do express HVR1 T-cell epitopes, suggesting that similar constraints govern HVR1-specific humoral and cellular immune responses. Moreover, some HVR1 mimotopes stimulate a multispecific CD4 + T-cell repertoire that effectively cross-reacts with HVR1 native sequences. This may significantly limit effects as a T-cell receptor (TCR) antagonist frequently exerted by natural HVR1-variants on HVR1-specific T-cell responses. In conclusion, these data lend strong support to using HVR1 mimotopes in vaccines designed to prevent replication of escape mutants. (H epatology 2003;38:653-663.)

Published
2003

18. Guidelines for the use of flow cytometry and cell sorting in immunological studies

Author

Guadalupe Herrera, Jens Geginat, Daryl Grummitt, Vincenzo Barnaba, Joanne Lannigan, Beate Rückert, Elisabetta Traggiai, Christian Münz, Susanne Melzer, Ari Waisman, Pratip K. Chattopadhyay, Jonas Hahn, T. Vincent Shankey, S Schmid, Julia Tornack, David W. Hedley, Paolo Dellabona, Jürgen Wienands, Ana Cumano, Ester B. M. Remmerswaal, Christopher A. Hunter, Van Duc Dang, Anis Larbi, Timothy P. Bushnell, Mor Gross, Wenjun Ouyang, Vera S. Donnenberg, Lilly Lopez, Holden T. Maecker, Jenny Mjösberg, Christina Stehle, Yanling Liu, Alan M. Stall, Anja E. Hauser, Yousuke Takahama, Mark C. Dessing, Gergely Toldi, Klaus Warnatz, Raghav Palankar, Sussan Nourshargh, Enrico Lugli, Bimba F. Hoyer, Pleun Hombrink, Bartek Rajwa, Sarah Warth, Isabel Panse, Rachael C. Walker, Silvia Piconese, Andrew Filby, Pärt Peterson, Kilian Schober, Silvia Della Bella, Leonie Wegener, Merle Stein, Anne Cooke, Alessandro Moretta, Deborah Kienhöfer, Andrea Cossarizza, Hyun-Dong Chang, Konrad von Volkmann, Jessica P. Houston, Mübeccel Akdis, Andreas Grützkau, Tristan Holland, Jakob Zimmermann, Jonni S. Moore, Dirk Mielenz, Iain B. McInnes, Bo Huang, Paulo Vieira, Thomas Kroneis, Tobit Steinmetz, Kerstin Juelke, Sharon Sanderson, James V. Watson, Srijit Khan, Sally A. Quataert, Winfried F. Pickl, Annika Wiedemann, Sara De Biasi, Andreas Radbruch, James B. Wing, Susann Müller, Ton N. Schumacher, Katy Rezvani, Gloria Martrus, Alexander Scheffold, Toralf Kaiser, Carlo Pucillo, Lara Gibellini, Anna Rubartelli, Qingyu Cheng, Luca Battistini, David Mirrer, David W. Galbraith, Giovanna Borsellino, Ryan R. Brinkman, Tim R. Mosmann, Laura G. Rico, Anita Dreher, Désirée Kunkel, Francesco Annunziato, Pia Kvistborg, Andrea Gori, Chiara Romagnani, Anat Shemer, Toshinori Nakayama, Francisco Sala-de-Oyanguren, Attila Tárnok, Alfonso Blanco, Anna Iannone, Giuseppe Matarese, Thomas Dörner, Virginia Litwin, Michael Lohoff, Petra Bacher, Jordi Petriz, Lorenzo Moretta, Götz R. A. Ehrhardt, Qianjun Zhang, Andrea Cavani, Barry Moran, Christian Maueröder, Immanuel Andrä, Dirk H. Busch, Joe Trotter, Timothy R D J Radstake, Stipan Jonjić, Fritz Melchers, Hans-Martin Jäck, Beatriz Jávega, Gerald Willimsky, Martin Büscher, Henrik E. Mei, Christine S. Falk, Zhigang Tian, Martin Herrmann, Alice Yue, Steffen Jung, Bart Everts, Frank A. Schildberg, John Bellamy Foster, Giovanna Lombardi, Milena Nasi, John P. Nolan, Todd A. Fehniger, Francesco Dieli, Steffen Schmitt, Andreas Dolf, A. Graham Pockley, Claudia Berek, Josef Spidlen, Megan K. Levings, Werner Müller, Baerbel Keller, René A. W. van Lier, Daisy Philips, Susanne Ziegler, Christian Kurts, Malgorzata J. Podolska, Jürgen Ruland, David Voehringer, Kenneth M. Murphy, Marlous van der Braber, Maria Dolores García-Godoy, Sabine Baumgart, Yi Zhao, Antonio Cosma, Falk Hiepe, Charlotte Esser, Pablo Engel, Marcello Veldhoen, Irmgard Förster, Amy E. Lovett-Racke, Günnur Deniz, Burkhard Ludewig, Esther Schimisky, Cristiano Scottà, Marcello Pinti, Jonathan Rebhahn, Regina Stark, Mario Clerici, Liping Yu, Shimon Sakaguchi, Derek Davies, Anna Katharina Simon, Lorenzo Cosmi, Gabriele Multhoff, Kamran Ghoreschi, Quirin Hammer, Henning Ulrich, J. Paul Robinson, Yvonne Samstag, Olivier Lantz, Hannes Stockinger, Xuetao Cao, Simon Fillatreau, David L. Haviland, Natalio Garbi, C. Neudörfl, Kingston H. G. Mills, Salvador Vento-Asturias, Christian Peth, Philip E. Boulais, Diether J. Recktenwald, Burkhard Becher, Tomas Kalina, Michael D. Leipold, Christoph Goettlinger, Gemma A. Foulds, Jane L. Grogan, Axel R. Schulz, James P. Di Santo, Matthias Schiemann, Michael D. Ward, Britta Engelhardt, Birgit Sawitzki, Annette Oxenius, Carl S. Goodyear, Salomé LeibundGut-Landmann, Wolfgang Beisker, Sue Chow, Carsten Watzl, Marie Follo, Erik Lubberts, Peter Wurst, Thomas Schüler, Andreas Diefenbach, Wolfgang Bauer, Hans-Dieter Volk, Luis E. Muñoz, Elmar Endl, Genny Del Zotto, José-Enrique O'Connor, Mairi McGrath, Paul S. Frenette, Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Cell Biology, Klinik für Dermatologie, Venerologie und Allergologie, Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Neuroimmunology Unit, Santa Lucia Foundation (IRCCS), Inorganic Chemistry II, Universität Bayreuth, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, Institut der Leibniz-Gemeinschaft, Berlin, Fondazione Santa Lucia (IRCCS), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Immunology, Chinese Academy of Medical Sciences, Fondazione Don Carlo Gnocchi, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Département d'Immunologie - Department of Immunology, Institut Pasteur [Paris], Charité Hospital, Humboldt-Universität zu Berlin, Universitat de Barcelona (UB), Rheumatologie, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Department of Histology and Embryology, University of Rijeka, Weizmann Institute of Science [Rehovot, Israël], Régulation des Infections Rétrovirales, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Institute of Virology [Zürich], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, Centre for Transplantation, King's College London (MRC), Guy's Hospital [London], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Institute, Heinrich Pette Institute [Hamburg], Institute of Translational Medicine, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Experimental Immunology, Helmholtz Centre for Infection Research (HZI), Viral Immunobiology, Universität Zürich [Zürich] = University of Zurich (UZH)-Institute of Experimental Immunology [Zurich], Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Department of Mathematics and Statistics, American University, William Harvey Research Institute, Barts and the London Medical School, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Osaka University [Osaka], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Institute for Cognitive Science, University of Osnabrueck, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Universität Leipzig [Leipzig], Institute of Immunology, School of Life Sciences-University of Science & Technology of China [Suzhou], Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Immunology, Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 (PROTEE), Université de Toulon (UTLN), Heinrich-Pette-Institut, Leibniz Institute for Experimental Virology, Enrico Lugli and Pratip K. Chattopadhyay were supported by grants from the Fondazione Cariplo (Grant Ricerca Biomedica 2012/0683), the Italian Ministry of Health (Bando Giovani Ricercatori GR-2011-02347324) and the European Union Marie Curie Career Integration Grant 322093 (all to E.L.). E.L. and P.K.C. are International Society for the Advancement of Cytometry (ISAC) Marylou Ingram scholars. Alice Yue and Ryan R. Brinkman were funded by Genome BC and NSERC. Klaus Warnatz received funding from the German Federal Ministry of Education and Research (BMBF 01EO1303) and the Deutsche Forschungsgemeinschaft (DECIDE, DFG WA 1597/4-1 and the TRR130). The Jung laboratory is supported by funds of the ERC and ISF. Henrik Mei is a 2017-2021 ISAC scholar. Antonio Cosma is supported by the French government program: 'Investissement d'avenir: Equipements d'Excellence' (EQUIPEX)-2010 FlowCyTech, Grant number: ANR-10-EQPX-02-01. Henrik Mei is supported by the Deutsche Forschungsgemeinschaft (DFG, grants Me3644/5-1 and TRR130/TP24)., Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Institut Pasteur [Paris] (IP), Humboldt University Of Berlin, Universität Bonn = University of Bonn, Università degli studi di Genova = University of Genoa (UniGe), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Universität Leipzig, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Obstetrics & Gynecology, Rheumatology, Pediatrics, Landsteiner Laboratory, Other departments, AII - Inflammatory diseases, Università di Modena e Reggio Emilia, DENOTHE Center-University of Florence, Santa Lucia Foundation ( IRCCS ), International Occultation Timing Association European Section ( IOTA ES ), Fondazione Santa Lucia ( IRCCS ), BC Cancer Agency ( BCCRC ) -British Columbia Cancer Agency Research Centre, Fondazione don Carlo Gnocchi, Fondazione IRCCS, Immunologie des Maladies Virales et Autoimmunes ( IMVA - U1184 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'Immunologie, Humboldt Universität zu Berlin, Universitat de Barcelona ( UB ), Charité, Weizmann Institute of Science, Université de Bonn, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Singapore Immunology Network ( SIgN ), Agency for Science Technology and Research, College of Food Science and Technology, Centre for Transplantation, King's College London ( MRC ), Erasmus MC University Medical Center, Helmholtz Centre for Environmental Research ( UFZ ), Helmholtz Centre for Infection Research ( HZI ), University of Zürich [Zürich] ( UZH ) -Institute of Experimental Immunology [Zurich], Ludwig-Maximilians-Universität München, Johannes Gutenberg - Universität Mainz ( JGU ), Medical University of Vienna, Lymphopoïèse, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Johannes Gutenberg - University of Mainz ( JGU ), Processus de Transfert et d'Echanges dans l'Environnement - EA 3819 ( PROTEE ), Université de Toulon ( UTLN ), Universita degli studi di Genova, Cossarizza, Andrea, Chang, Hyun-Dong, Radbruch, Andrea, Akdis, Mübeccel, Andrä, Immanuel, Annunziato, Francesco, Bacher, Petra, Barnaba, Vincenzo, Battistini, Luca, Bauer, Wolfgang M., Baumgart, Sabine, Becher, Burkhard, Beisker, Wolfgang, Berek, Claudia, Blanco, Alfonso, Borsellino, Giovanna, Boulais, Philip E., Brinkman, Ryan R., Büscher, Martin, Busch, Dirk H., Bushnell, Timothy P., Cao, Xuetao, Cavani, Andrea, Chattopadhyay, Pratip K., Cheng, Qingyu, Chow, Sue, Clerici, Mario, Cooke, Anne, Cosma, Antonio, Cosmi, Lorenzo, Cumano, Ana, Dang, Van Duc, Davies, Derek, De Biasi, Sara, Del Zotto, Genny, Della Bella, Silvia, Dellabona, Paolo, Deniz, Günnur, Dessing, Mark, Diefenbach, Andrea, Di Santo, Jame, Dieli, Francesco, Dolf, Andrea, Donnenberg, Vera S., Dörner, Thoma, Ehrhardt, Götz R. A., Endl, Elmar, Engel, Pablo, Engelhardt, Britta, Esser, Charlotte, Everts, Bart, Dreher, Anita, Falk, Christine S., Fehniger, Todd A., Filby, Andrew, Fillatreau, Simon, Follo, Marie, Förster, Irmgard, Foster, John, Foulds, Gemma A., Frenette, Paul S., Galbraith, David, Garbi, Natalio, García-Godoy, Maria Dolore, Geginat, Jen, Ghoreschi, Kamran, Gibellini, Lara, Goettlinger, Christoph, Goodyear, Carl S., Gori, Andrea, Grogan, Jane, Gross, Mor, Grützkau, Andrea, Grummitt, Daryl, Hahn, Jona, Hammer, Quirin, Hauser, Anja E., Haviland, David L., Hedley, David, Herrera, Guadalupe, Herrmann, Martin, Hiepe, Falk, Holland, Tristan, Hombrink, Pleun, Houston, Jessica P., Hoyer, Bimba F., Huang, Bo, Hunter, Christopher A., Iannone, Anna, Jäck, Hans-Martin, Jávega, Beatriz, Jonjic, Stipan, Juelke, Kerstin, Jung, Steffen, Kaiser, Toralf, Kalina, Toma, Keller, Baerbel, Khan, Srijit, Kienhöfer, Deborah, Kroneis, Thoma, Kunkel, Désirée, Kurts, Christian, Kvistborg, Pia, Lannigan, Joanne, Lantz, Olivier, Larbi, Ani, LeibundGut-Landmann, Salome, Leipold, Michael D., Levings, Megan K., Litwin, Virginia, Liu, Yanling, Lohoff, Michael, Lombardi, Giovanna, Lopez, Lilly, Lovett-Racke, Amy, Lubberts, Erik, Ludewig, Burkhard, Lugli, Enrico, Maecker, Holden T., Martrus, Glòria, Matarese, Giuseppe, Maueröder, Christian, Mcgrath, Mairi, Mcinnes, Iain, Mei, Henrik E., Melchers, Fritz, Melzer, Susanne, Mielenz, Dirk, Mills, Kingston, Mirrer, David, Mjösberg, Jenny, Moore, Jonni, Moran, Barry, Moretta, Alessandro, Moretta, Lorenzo, Mosmann, Tim R., Müller, Susann, Müller, Werner, Münz, Christian, Multhoff, Gabriele, Munoz, Luis Enrique, Murphy, Kenneth M., Nakayama, Toshinori, Nasi, Milena, Neudörfl, Christine, Nolan, John, Nourshargh, Sussan, O'Connor, José-Enrique, Ouyang, Wenjun, Oxenius, Annette, Palankar, Raghav, Panse, Isabel, Peterson, Pärt, Peth, Christian, Petriz, Jordi, Philips, Daisy, Pickl, Winfried, Piconese, Silvia, Pinti, Marcello, Pockley, A. Graham, Podolska, Malgorzata Justyna, Pucillo, Carlo, Quataert, Sally A., Radstake, Timothy R. D. J., Rajwa, Bartek, Rebhahn, Jonathan A., Recktenwald, Diether, Remmerswaal, Ester B. M., Rezvani, Katy, Rico, Laura G., Robinson, J. Paul, Romagnani, Chiara, Rubartelli, Anna, Ruckert, Beate, Ruland, Jürgen, Sakaguchi, Shimon, Sala-de-Oyanguren, Francisco, Samstag, Yvonne, Sanderson, Sharon, Sawitzki, Birgit, Scheffold, Alexander, Schiemann, Matthia, Schildberg, Frank, Schimisky, Esther, Schmid, Stephan A., Schmitt, Steffen, Schober, Kilian, Schüler, Thoma, Schulz, Axel Ronald, Schumacher, Ton, Scotta, Cristiano, Shankey, T. Vincent, Shemer, Anat, Simon, Anna-Katharina, Spidlen, Josef, Stall, Alan M., Stark, Regina, Stehle, Christina, Stein, Merle, Steinmetz, Tobit, Stockinger, Hanne, Takahama, Yousuke, Tarnok, Attila, Tian, Zhigang, Toldi, Gergely, Tornack, Julia, Traggiai, Elisabetta, Trotter, Joe, Ulrich, Henning, van der Braber, Marlou, van Lier, René A. W., Veldhoen, Marcello, Vento-Asturias, Salvador, Vieira, Paulo, Voehringer, David, Volk, Hans-Dieter, von Volkmann, Konrad, Waisman, Ari, Walker, Rachael, Ward, Michael D., Warnatz, Klau, Warth, Sarah, Watson, James V., Watzl, Carsten, Wegener, Leonie, Wiedemann, Annika, Wienands, Jürgen, Willimsky, Gerald, Wing, Jame, Wurst, Peter, Yu, Liping, Yue, Alice, Zhang, Qianjun, Zhao, Yi, Ziegler, Susanne, Zimmermann, Jakob, Cossarizza, A., Chang, H., Radbruch, A., Akdis, M., Andrã¤, I., Annunziato, F., Bacher, P., Barnaba, V., Battistini, L., Bauer, W., Baumgart, S., Becher, B., Beisker, W., Berek, C., Blanco, A., Borsellino, G., Boulais, P., Brinkman, R., Bã¼scher, M., Busch, D., Bushnell, T., Cao, X., Cavani, A., Chattopadhyay, P., Cheng, Q., Chow, S., Clerici, M., Cooke, A., Cosma, A., Cosmi, L., Cumano, A., Dang, V., Davies, D., De Biasi, S., Del Zotto, G., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Diefenbach, A., Di Santo, J., Dieli, F., Dolf, A., Donnenberg, V., Dã¶rner, T., Ehrhardt, G., Endl, E., Engel, P., Engelhardt, B., Esser, C., Everts, B., Dreher, A., Falk, C., Fehniger, T., Filby, A., Fillatreau, S., Follo, M., Fã¶rster, I., Foster, J., Foulds, G., Frenette, P., Galbraith, D., Garbi, N., García-Godoy, M., Geginat, J., Ghoreschi, K., Gibellini, L., Goettlinger, C., Goodyear, C., Gori, A., Grogan, J., Gross, M., Grã¼tzkau, A., Grummitt, D., Hahn, J., Hammer, Q., Hauser, A., Haviland, D., Hedley, D., Herrera, G., Herrmann, M., Hiepe, F., Holland, T., Hombrink, P., Houston, J., Hoyer, B., Huang, B., Hunter, C., Iannone, A., Jã¤ck, H., Jã¡vega, B., Jonjic, S., Juelke, K., Jung, S., Kaiser, T., Kalina, T., Keller, B., Khan, S., Kienhã¶fer, D., Kroneis, T., Kunkel, D., Kurts, C., Kvistborg, P., Lannigan, J., Lantz, O., Larbi, A., LeibundGut-Landmann, S., Leipold, M., Levings, M., Litwin, V., Liu, Y., Lohoff, M., Lombardi, G., Lopez, L., Lovett-Racke, A., Lubberts, E., Ludewig, B., Lugli, E., Maecker, H., Martrus, G., Matarese, G., Mauerã¶der, C., Mcgrath, M., Mcinnes, I., Mei, H., Melchers, F., Melzer, S., Mielenz, D., Mills, K., Mirrer, D., Mjã¶sberg, J., Moore, J., Moran, B., Moretta, A., Moretta, L., Mosmann, T., Mã¼ller, S., Mã¼ller, W., Mã¼nz, C., Multhoff, G., Munoz, L., Murphy, K., Nakayama, T., Nasi, M., Neudã¶rfl, C., Nolan, J., Nourshargh, S., O'Connor, J., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Peterson, P., Peth, C., Petriz, J., Philips, D., Pickl, W., Piconese, S., Pinti, M., Pockley, A., Podolska, M., Pucillo, C., Quataert, S., Radstake, T., Rajwa, B., Rebhahn, J., Recktenwald, D., Remmerswaal, E., Rezvani, K., Rico, L., Robinson, J., Romagnani, C., Rubartelli, A., Ruckert, B., Ruland, J., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sawitzki, B., Scheffold, A., Schiemann, M., Schildberg, F., Schimisky, E., Schmid, S., Schmitt, S., Schober, K., Schã¼ler, T., Schulz, A., Schumacher, T., Scotta, C., Shankey, T., Shemer, A., Simon, A., Spidlen, J., Stall, A., Stark, R., Stehle, C., Stein, M., Steinmetz, T., Stockinger, H., Takahama, Y., Tarnok, A., Tian, Z., Toldi, G., Tornack, J., Traggiai, E., Trotter, J., Ulrich, H., van der Braber, M., van Lier, R., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H., von Volkmann, K., Waisman, A., Walker, R., Ward, M., Warnatz, K., Warth, S., Watson, J., Watzl, C., Wegener, L., Wiedemann, A., Wienands, J., Willimsky, G., Wing, J., Wurst, P., Liping, Y., Yue, A., Zhang, Q., Zhao, Y., Ziegler, S., and Zimmermann, J.

Subjects
0301 basic medicine, T-Lymphocytes, Cell Separation, T cell precursors, 0302 clinical medicine, Immunophenotyping, Human lymphopoiesis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Non-U.S. Gov't, Immunologic Technique, medicine.diagnostic_test, Research Support, Non-U.S. Gov't, virus diseases, hemic and immune systems, False Positive Reaction, Cell sorting, Flow Cytometry, natural killer and innate lymphoid cells differentiation, 3. Good health, Research Design, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human, Quality Control, medicine.drug_class, Immunology, Animals, Cell Proliferation, DNA, False Positive Reactions, Humans, RNA, Software, Guidelines as Topic, Immunologic Techniques, chemical and pharmacologic phenomena, Computational biology, Biology, Monoclonal antibody, Research Support, Article, Flow cytometry, N.I.H, 03 medical and health sciences, Immune system, Research Support, N.I.H., Extramural, medicine, early lymphoid progenitors, Journal Article, Mass cytometry, IMUNOLOGIA, Animal, Extramural, B cell ontogeny, 030104 developmental biology, T-Lymphocyte, Cytometry, 030215 immunology
Abstract

The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

Published
2017

19. Hypervariable region 1 variant acting as TCR antagonist affects hepatitis C virus-specific CD4+ T cell repertoire by favoring CD95-mediated apoptosis

Author

Cristiano Scottà, Loredana Frasca, Enza Piccolella, Luigi Racioppi, Loretta Tuosto, Anna Maria Masci, Scotta, C, Tuosto, L, Masci, Am, Racioppi, Luigi, Piccolella, E, and Frasca, L.

Subjects
Agonist, CD4-Positive T-Lymphocytes, medicine.drug_class, viruses, T cell, Receptors, Antigen, T-Cell, alpha-beta, Immunology, Population, Down-Regulation, Epitopes, T-Lymphocyte, Apoptosis, Hepacivirus, Biology, Lymphocyte Activation, Interleukin 21, Viral Proteins, Immune system, T-Lymphocyte Subsets, medicine, Immunology and Allergy, Cytotoxic T cell, Humans, fas Receptor, education, Antigens, Viral, spectratyping, Cells, Cultured, Serpins, Cell Proliferation, education.field_of_study, T-cell receptor, virus diseases, Cell Biology, Virology, Molecular biology, digestive system diseases, medicine.anatomical_structure, inflammation, HCV, CD8
Abstract

We have described previously that hy- pervariable region 1 (HVR1) variants of hepatitis C virus (HCV) frequently act as T cell receptor (TCR) antagonists for HVR1-specific helper T cells. These naturally occurring HVR1-antagonistic sequences interfered with the effects of HVR1-agonistic se- quences such as TCR down-regulation and early activatory signals. By taking advantage of these findings, in this paper, we have analyzed the fate of these HVR1-specific antagonized CD4 T cells. We present the evidence that TCR antagonism renders agonist-activated T cells susceptible to bystander CD95-mediated killing by suppressing the expres- sion of cellular Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitor proteins. To verify whether the TCR repertoire of a HVR1-specific T cell population could be modi- fied consequently, we used a HVR1-agonistic se- quence to induce in vitro CD4 T cells and another HVR1 sequence with antagonistic property to me- diate suppressive phenomena. HVR1-specific T cells were cultured with the agonist alone or with the agonist plus the antagonist. HVR1 specificity and T cell repertoires were followed over time by analyzing TCR -variable gene segment by "spec- tratyping". The results showed that the specificity for the agonist was rapidly spoiled after culture in the presence of the antagonist, and the TCR rep- ertoire was strongly modified as a result of CD95- mediated apoptosis of agonist-specific clonal ex- pansions. These data support the hypothesis that in HCV infection, the generation of TCR antagonists may reshape the T cell repertoire, representing an efficacious immune evasion strategy of a highly mutant pathogen. J. Leukoc. Biol. 78: 372-382; 2005.

Published
2005

20. The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review.

Author

Headen K, Jakaite V, Mesaric VA, Scotta C, Lombardi G, Nicolaides KH, and Shangaris P

Subjects
Humans, Pregnancy, Female, Animals, Pre-Eclampsia immunology, Pre-Eclampsia therapy, Immune Tolerance, T-Lymphocytes, Regulatory immunology, Hypertension, Pregnancy-Induced immunology, Hypertension, Pregnancy-Induced therapy
Abstract

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Published
2024
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21. Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive.

Author

Mohseni YR, Saleem A, Tung SL, Dudreuilh C, Lang C, Peng Q, Volpe A, Adigbli G, Cross A, Hester J, Farzaneh F, Scotta C, Lechler RI, Issa F, Fruhwirth GO, and Lombardi G

Subjects
Gene Order, Genetic Engineering, Genetic Vectors genetics, Humans, Interleukin-10 metabolism, Receptors, Chimeric Antigen immunology, Gene Expression, Immunomodulation, Interleukin-10 genetics, Phenotype, Receptors, Chimeric Antigen genetics, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism
Abstract

Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation., (© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Published
2021
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22. Feasibility, long-term safety, and immune monitoring of regulatory T cell therapy in living donor kidney transplant recipients.

Author

Harden PN, Game DS, Sawitzki B, Van der Net JB, Hester J, Bushell A, Issa F, Brook MO, Alzhrani A, Schlickeiser S, Scotta C, Petchey W, Streitz M, Blancho G, Tang Q, Markmann J, Lechler RI, Roberts ISD, Friend PJ, Hilton R, Geissler EK, Wood KJ, and Lombardi G

Subjects
Feasibility Studies, Graft Rejection etiology, Graft Rejection prevention & control, Humans, Immunosuppressive Agents therapeutic use, Living Donors, Monitoring, Immunologic, T-Lymphocytes, Regulatory, Kidney Transplantation
Abstract

Short-term outcomes in kidney transplantation are marred by progressive transplant failure and mortality secondary to immunosuppression toxicity. Immune modulation with autologous polyclonal regulatory T cell (Treg) therapy may facilitate immunosuppression reduction promoting better long-term clinical outcomes. In a Phase I clinical trial, 12 kidney transplant recipients received 1-10 × 10 6 Treg per kg at Day +5 posttransplantation in lieu of induction immunosuppression (Treg Therapy cohort). Nineteen patients received standard immunosuppression (Reference cohort). Primary outcomes were rejection-free and patient survival. Patient and transplant survival was 100%; acute rejection-free survival was 100% in the Treg Therapy versus 78.9% in the reference cohort at 48 months posttransplant. Treg therapy revealed no excess safety concerns. Four patients in the Treg Therapy cohort had mycophenolate mofetil withdrawn successfully and remain on tacrolimus monotherapy. Treg infusion resulted in a long-lasting dose-dependent increase in peripheral blood Tregs together with an increase in marginal zone B cell numbers. We identified a pretransplantation immune phenotype suggesting a high risk of unsuccessful ex-vivo Treg expansion. Autologous Treg therapy is feasible, safe, and is potentially associated with a lower rejection rate than standard immunosuppression. Treg therapy may provide an exciting opportunity to minimize immunosuppression therapy and improve long-term outcomes., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Published
2021
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23. Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment.

Author

Jacob J, Nadkarni S, Volpe A, Peng Q, Tung SL, Hannen RF, Mohseni YR, Scotta C, Marelli-Berg FM, Lechler RI, Smyth LA, Fruhwirth GO, and Lombardi G

Abstract

Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo . Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1 + innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans., Competing Interests: G.L. is a co-founder of Quell Therapeutics. S.L.T. and Y.R.M. are employed by Quell Therapeutics (all data contributed by S.L.T. and Y.R.M. were collected before being employed by Quell Therapeutics)., (© 2021 The Authors.)

Published
2020
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24. Correction of Defective T-Regulatory Cells From Patients With Crohn's Disease by Ex Vivo Ligation of Retinoic Acid Receptor-α.

Author

Goldberg R, Scotta C, Cooper D, Nissim-Eliraz E, Nir E, Tasker S, Irving PM, Sanderson J, Lavender P, Ibrahim F, Corcoran J, Prevost T, Shpigel NY, Marelli-Berg F, Lombardi G, and Lord GM

Subjects
Adult, Animals, Antineoplastic Agents pharmacology, Case-Control Studies, Cell Culture Techniques, Cell Movement drug effects, Cells, Cultured, Female, Forkhead Transcription Factors metabolism, Gene Expression drug effects, Heterografts, Humans, Immunosuppressive Agents pharmacology, Integrins genetics, Intestinal Mucosa immunology, Intestinal Mucosa transplantation, L-Selectin metabolism, Lymphocyte Activation, Male, Mice, Mice, SCID, Middle Aged, Organic Chemicals pharmacology, Sirolimus pharmacology, T-Lymphocytes, Regulatory immunology, Transcriptome drug effects, Tretinoin pharmacology, Crohn Disease immunology, Integrins metabolism, Retinoic Acid Receptor alpha agonists, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory metabolism
Abstract

Background & Aims: Crohn's disease (CD) is characterized by an imbalance of effector and regulatory T cells in the intestinal mucosa. The efficacy of anti-adhesion therapies led us to investigate whether impaired trafficking of T-regulatory (Treg) cells contributes to the pathogenesis of CD. We also investigated whether proper function could be restored to Treg cells by ex vivo expansion in the presence of factors that activate their regulatory activities., Methods: We measured levels of the integrin α4β7 on Treg cells isolated from peripheral blood or lamina propria of patients with CD and healthy individuals (controls). Treg cells were expanded ex vivo and incubated with rapamycin with or without agonists of the retinoic acid receptor-α (RARA), and their gene expression profiles were analyzed. We also studied the cells in cytokine challenge, suppression, and flow chamber assays and in SCID mice with human intestinal xenografts., Results: We found that Treg cells from patients with CD express lower levels of the integrin α4β7 than Treg cells from control patients. The pathway that regulates the expression of integrin subunit α is induced by retinoic acid (RA). Treg cells from patients with CD incubated with rapamycin and an agonist of RARA (RAR568) expressed high levels of integrin α4β7, as well as CD62L and FOXP3, compared with cells incubated with rapamycin or rapamycin and all-trans retinoic acid. These Treg cells had increased suppressive activities in assays and migrated under conditions of shear flow; they did not produce inflammatory cytokines, and RAR568 had no effect on cell stability or lineage commitment. Fluorescently labeled Treg cells incubated with RAR568 were significantly more likely to traffic to intestinal xenografts than Treg cells expanded in control medium., Conclusions: Treg cells from patients with CD express lower levels of the integrin α4β7 than Treg cells from control patients. Incubation of patients' ex vivo expanded Treg cells with rapamycin and an RARA agonist induced expression of α4β7 and had suppressive and migratory activities in culture and in intestinal xenografts in mice. These cells might be developed for treatment of CD. ClinicalTrials.gov, Number: NCT03185000., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2019
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25. Guidelines for the use of flow cytometry and cell sorting in immunological studies.

Author

Cossarizza A, Chang HD, Radbruch A, Akdis M, Andrä I, Annunziato F, Bacher P, Barnaba V, Battistini L, Bauer WM, Baumgart S, Becher B, Beisker W, Berek C, Blanco A, Borsellino G, Boulais PE, Brinkman RR, Büscher M, Busch DH, Bushnell TP, Cao X, Cavani A, Chattopadhyay PK, Cheng Q, Chow S, Clerici M, Cooke A, Cosma A, Cosmi L, Cumano A, Dang VD, Davies D, De Biasi S, Del Zotto G, Della Bella S, Dellabona P, Deniz G, Dessing M, Diefenbach A, Di Santo J, Dieli F, Dolf A, Donnenberg VS, Dörner T, Ehrhardt GRA, Endl E, Engel P, Engelhardt B, Esser C, Everts B, Dreher A, Falk CS, Fehniger TA, Filby A, Fillatreau S, Follo M, Förster I, Foster J, Foulds GA, Frenette PS, Galbraith D, Garbi N, García-Godoy MD, Geginat J, Ghoreschi K, Gibellini L, Goettlinger C, Goodyear CS, Gori A, Grogan J, Gross M, Grützkau A, Grummitt D, Hahn J, Hammer Q, Hauser AE, Haviland DL, Hedley D, Herrera G, Herrmann M, Hiepe F, Holland T, Hombrink P, Houston JP, Hoyer BF, Huang B, Hunter CA, Iannone A, Jäck HM, Jávega B, Jonjic S, Juelke K, Jung S, Kaiser T, Kalina T, Keller B, Khan S, Kienhöfer D, Kroneis T, Kunkel D, Kurts C, Kvistborg P, Lannigan J, Lantz O, Larbi A, LeibundGut-Landmann S, Leipold MD, Levings MK, Litwin V, Liu Y, Lohoff M, Lombardi G, Lopez L, Lovett-Racke A, Lubberts E, Ludewig B, Lugli E, Maecker HT, Martrus G, Matarese G, Maueröder C, McGrath M, McInnes I, Mei HE, Melchers F, Melzer S, Mielenz D, Mills K, Mirrer D, Mjösberg J, Moore J, Moran B, Moretta A, Moretta L, Mosmann TR, Müller S, Müller W, Münz C, Multhoff G, Munoz LE, Murphy KM, Nakayama T, Nasi M, Neudörfl C, Nolan J, Nourshargh S, O'Connor JE, Ouyang W, Oxenius A, Palankar R, Panse I, Peterson P, Peth C, Petriz J, Philips D, Pickl W, Piconese S, Pinti M, Pockley AG, Podolska MJ, Pucillo C, Quataert SA, Radstake TRDJ, Rajwa B, Rebhahn JA, Recktenwald D, Remmerswaal EBM, Rezvani K, Rico LG, Robinson JP, Romagnani C, Rubartelli A, Ruckert B, Ruland J, Sakaguchi S, Sala-de-Oyanguren F, Samstag Y, Sanderson S, Sawitzki B, Scheffold A, Schiemann M, Schildberg F, Schimisky E, Schmid SA, Schmitt S, Schober K, Schüler T, Schulz AR, Schumacher T, Scotta C, Shankey TV, Shemer A, Simon AK, Spidlen J, Stall AM, Stark R, Stehle C, Stein M, Steinmetz T, Stockinger H, Takahama Y, Tarnok A, Tian Z, Toldi G, Tornack J, Traggiai E, Trotter J, Ulrich H, van der Braber M, van Lier RAW, Veldhoen M, Vento-Asturias S, Vieira P, Voehringer D, Volk HD, von Volkmann K, Waisman A, Walker R, Ward MD, Warnatz K, Warth S, Watson JV, Watzl C, Wegener L, Wiedemann A, Wienands J, Willimsky G, Wing J, Wurst P, Yu L, Yue A, Zhang Q, Zhao Y, Ziegler S, and Zimmermann J

Subjects
Animals, Cell Proliferation, Cell Separation, False Positive Reactions, Flow Cytometry, Humans, Immunophenotyping, Quality Control, Research Design, Software, DNA analysis, Guidelines as Topic, Immunologic Techniques, RNA analysis, T-Lymphocytes cytology
Published
2017
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26. Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation.

Author

Safinia N, Scotta C, Vaikunthanathan T, Lechler RI, and Lombardi G

Abstract

Regulatory T cells (Tregs) play an important role in immunoregulation and have been shown in animal models to promote transplantation tolerance and curb autoimmunity following their adoptive transfer. The safety and potential therapeutic efficacy of these cells has already been reported in Phase I trials of bone-marrow transplantation and type I diabetes, the success of which has motivated the broadened application of these cells in solid-organ transplantation. Despite major advances in the clinical translation of these cells, there are still key questions to be addressed to ensure that Tregs attest their reputation as ideal candidates for tolerance induction. In this review, we will discuss the unique traits of Tregs that have attracted such fame in the arena of tolerance induction. We will outline the protocols used for their ex vivo expansion and discuss the future directions of Treg cell therapy. In this regard, we will review the concept of Treg heterogeneity, the desire to isolate and expand a functionally superior Treg population and report on the effect of differing culture conditions. The relevance of Treg migratory capacity will also be discussed together with methods of in vivo visualization of the infused cells. Moreover, we will highlight key advances in the identification and expansion of antigen-specific Tregs and discuss their significance for cell therapy application. We will also summarize the clinical parameters that are of importance, alongside cell manufacture, from the choice of immunosuppression regimens to the number of injections in order to direct the success of future efficacy trials of Treg cell therapy. Years of research in the field of tolerance have seen an accumulation of knowledge and expertise in the field of Treg biology. This perpetual progression has been the driving force behind the many successes to date and has put us now within touching distance of our ultimate success, immunological tolerance.

Published
2015
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27. Whole-cell MALDI-TOF mass spectrometry and multilocus sequence analysis in the discrimination of Pseudomonas stutzeri populations: three novel genomovars.

Author

Scotta C, Gomila M, Mulet M, Lalucat J, and García-Valdés E

Subjects
Environmental Microbiology, Genetic Variation, Humans, Molecular Sequence Data, Phylogeny, Pseudomonas stutzeri classification, Pseudomonas stutzeri genetics, Multilocus Sequence Typing methods, Pseudomonas Infections microbiology, Pseudomonas stutzeri chemistry, Pseudomonas stutzeri isolation & purification, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Abstract

Pseudomonas stutzeri is a widely distributed species with very high genetic diversity and metabolic capacities, occupying many diverse ecological niches. A collection of 229 P. stutzeri strains isolated from different habitats and geographical locations has been previously characterised phylogenetically by rpoD gene sequencing analysis and in the present study 172 of them phenotypically by whole-cell MALDI-TOF mass spectrometry. Fifty-five strains were further analysed by multilocus sequencing analysis to determine the phylogenetic population structure. Both methods showed coherence in strain grouping; 226 strains were allocated in the 18 genomovars known presently. The remaining three strains are proposed as references for three novel genomovars in the species. The correlation and usefulness of sequence-based phylogenetic analysis and whole-cell MALDI-TOF mass spectrometry, which are essential for autoecological studies in microbial ecology, is discussed for the differentiation of P. stutzeri populations.

Published
2013
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28. CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner.

Author

Afzali B, Mitchell PJ, Edozie FC, Povoleri GA, Dowson SE, Demandt L, Walter G, Canavan JB, Scotta C, Menon B, Chana PS, Khamri W, Kordasti SY, Heck S, Grimbacher B, Tree T, Cope AP, Taams LS, Lechler RI, John S, and Lombardi G

Subjects
Adult, Aged, CD4 Antigens biosynthesis, Cells, Cultured, Female, Forkhead Transcription Factors biosynthesis, Humans, Interleukin-1beta metabolism, Interleukin-2 Receptor alpha Subunit biosynthesis, Interleukin-6 metabolism, Interleukin-7 Receptor alpha Subunit biosynthesis, Leukocyte Common Antigens biosynthesis, Lymphocyte Activation, Male, Middle Aged, NK Cell Lectin-Like Receptor Subfamily B immunology, STAT3 Transcription Factor genetics, Interleukin-17 biosynthesis, NK Cell Lectin-Like Receptor Subfamily B metabolism, STAT3 Transcription Factor metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism
Abstract

Treg cells are critical for the prevention of autoimmune diseases and are thus prime candidates for cell-based clinical therapy. However, human Treg cells are "plastic", and are able to produce IL-17 under inflammatory conditions. Here, we identify and characterize the human Treg subpopulation that can be induced to produce IL-17 and identify its mechanisms. We confirm that a subpopulation of human Treg cells produces IL-17 in vitro when activated in the presence of IL-1β, but not IL-6. "IL-17 potential" is restricted to population III (CD4(+) CD25(hi) CD127(lo) CD45RA(-) ) Treg cells expressing the natural killer cell marker CD161. We show that these cells are functionally as suppressive and have similar phenotypic/molecular characteristics to other subpopulations of Treg cells and retain their suppressive function following IL-17 induction. Importantly, we find that IL-17 production is STAT3 dependent, with Treg cells from patients with STAT3 mutations unable to make IL-17. Finally, we show that CD161(+) population III Treg cells accumulate in inflamed joints of patients with inflammatory arthritis and are the predominant IL-17-producing Treg-cell population at these sites. As IL-17 production from this Treg-cell subpopulation is not accompanied by a loss of regulatory function, in the context of cell therapy, exclusion of these cells from the cell product may not be necessary., (© 2013 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.)

Published
2013
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29. Concordance between whole-cell matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry and multilocus sequence analysis approaches in species discrimination within the genus Pseudomonas.

Author

Mulet M, Gomila M, Scotta C, Sánchez D, Lalucat J, and García-Valdés E

Subjects
Bacterial Proteins chemistry, Bacterial Proteins genetics, Cluster Analysis, DNA, Bacterial chemistry, DNA, Bacterial genetics, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, Molecular Sequence Data, Phylogeny, Proteome analysis, Pseudomonas chemistry, Pseudomonas genetics, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, Multilocus Sequence Typing methods, Pseudomonas classification, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Abstract

Multilocus sequence analysis (MLSA) is one of the most accepted methods for the phylogenetic assignation of Pseudomonas strains to their corresponding species. Furthermore, updated databases are essential for correct bacterial identification and the number of Pseudomonas species is increasing continuously. Currently, 127 species are validly described in Euzéby's List of Species with Standing in Nomenclature, and 29 novel species have been described since the publication of the last comprehensive MLSA phylogenetic study based on the sequences of the 16S rDNA, gyrB, rpoB and rpoD genes. Therefore, an update of the sequence database is presented, together with the analysis of the phylogeny of the genus Pseudomonas. Whole-cell matrix-assisted laser-desorption/ionization time-of-flight (WC-MALDI-TOF) mass spectrometry (MS) analysis has been applied very recently to the identification of bacteria and is considered to be a fast and reliable method. A total of 133 type strains of the recognized species and subspecies in the genus Pseudomonas, together with other representative strains, were analyzed using this new technique, and the congruence between the WC-MALDI-TOF MS and MLSA techniques was assessed for the discrimination and correct species identification of the strains. The utility of both methods in the identification of environmental and clinical strains is discussed., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Published
2012
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30. Environmental microbiota represents a natural reservoir for dissemination of clinically relevant metallo-beta-lactamases.

Author

Scotta C, Juan C, Cabot G, Oliver A, Lalucat J, Bennasar A, and Albertí S

Subjects
Agrobacterium tumefaciens enzymology, Agrobacterium tumefaciens genetics, Enterobacter enzymology, Enterobacter genetics, Hospitals, Integrons genetics, Ochrobactrum anthropi enzymology, Ochrobactrum anthropi genetics, Plasmids genetics, Pseudomonas enzymology, Pseudomonas genetics, Pseudomonas aeruginosa enzymology, Pseudomonas aeruginosa genetics, Sewage microbiology, Water Microbiology, beta-Lactamases genetics
Abstract

A total of 10 metallo-β-lactamase-producing isolates of six different species, including Brevundimonas diminuta (n = 3), Rhizobium radiobacter (n = 2), Pseudomonas monteilii (n = 1), Pseudomonas aeruginosa (n = 2), Ochrobactrum anthropi (n = 1), and Enterobacter ludwigii (n = 1), were detected in the sewage water of a hospital. The presence of bla(VIM-13) associated with a Tn1721-class 1 integron structure was detected in all but one of the isolates (E. ludwigii, which produced VIM-2), and in two of them (R. radiobacter), this structure was located on a plasmid, suggesting that environmental bacteria represent a reservoir for the dissemination of clinically relevant metallo-β-lactamase genes.

Published
2011
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31. Taxonomic characterisation of ceftazidime-resistant Brevundimonas isolates and description of Brevundimonas faecalis sp. nov.

Author

Scotta C, Bennasar A, Moore ER, Lalucat J, and Gomila M

Subjects
Anti-Bacterial Agents pharmacology, Base Sequence, Caulobacteraceae drug effects, Caulobacteraceae genetics, Caulobacteraceae isolation & purification, DNA, Bacterial genetics, DNA, Ribosomal genetics, Drug Resistance, Bacterial, Genes, Bacterial, Genetic Variation, Microbial Sensitivity Tests, Molecular Sequence Data, Phylogeny, Sewage microbiology, Spain, Caulobacteraceae classification, Ceftazidime pharmacology, Water Microbiology
Abstract

Three ceftazidime-resistant strains isolated from the sewage water of a municipal hospital in Palma de Mallorca, Spain, were analysed phenotypically and genotypically to clarify their taxonomic positions. Sequence determinations and phylogenetic analyses of the 16S rRNA genes indicated that strains CS20.3(T), CS39 and CS41 were affiliated with the species of the alphaproteobacterial genus Brevundimonas, most closely related to B. bullata, B. diminuta, B. naejangsanensis and B. terrae. Additional sequences analyses of the ITS1 region of the rRNA operon and the genes for the housekeeping enzymes DNA gyrase β-subunit and RNA polymerase β-subunit, genomic DNA-DNA hybridisation similarities, cell fatty acid profiles and physiological and biochemical characterizations supported the recognition of CS20.3(T) (CCUG 58127(T)=CECT 7729(T)) as a distinct and novel species, for which the name Brevundimonas faecalis sp. nov. is proposed. Strains CS39 and CS41 were ascribed to the species B. diminuta., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Published
2011
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32. Cell therapy to promote transplantation tolerance: a winning strategy?

Author

Lombardi G, Sagoo P, Scotta C, Fazekasova H, Smyth L, Tsang J, Afzali B, and Lechler R

Subjects
Animals, Blood Transfusion, Autologous, Cell Proliferation, Clinical Trials as Topic, Graft Rejection prevention & control, Humans, Isoantigens immunology, Mice, Cell- and Tissue-Based Therapy, Graft Rejection immunology, Organ Transplantation, T-Lymphocytes, Regulatory immunology, Transplantation Tolerance
Abstract

Organ transplantation is currently the only effective treatment for end-stage organ failure. However, success is limited by the immune response of the recipient to allogeneic tissues (recognized by the direct and indirect alloresponses) and by the morbidity and mortality associated with the immunosuppressive drugs that are used to control alloimmunity. One solution to these problems is the induction of immunological tolerance. In our laboratory, we have selected two strategies to achieve this goal. The first is to expand and/or generate Tregs directly in vivo using infusions of 'tolerogenic' DCs into patients; the second is to purify Tregs from the blood of patients on the waiting list for a transplant, enrich and expand these cells in vitro and then inject back in vivo after transplantation. Here, we have summarized our results both in the murine and human systems on the use of Treg-based strategies to induce tolerance to the transplanted organs.

Published
2011
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33. Entropically-driven binding of mithramycin in the minor groove of C/G-rich DNA sequences.

Author

Barceló F, Scotta C, Ortiz-Lombardía M, Méndez C, Salas JA, and Portugal J

Subjects
Calorimetry, Dialysis, Hot Temperature, Models, Molecular, Nucleic Acid Conformation, Nucleic Acid Denaturation, Plicamycin chemistry, Spectrophotometry, Ultraviolet, Antibiotics, Antineoplastic chemistry, DNA chemistry, Entropy, GC Rich Sequence, Plicamycin analogs & derivatives
Abstract

The antitumour antibiotic mithramycin A (MTA) is a DNA minor-groove binding ligand. It binds to C/G-rich tracts as a dimer that forms in the presence of divalent cations such as Mg(2+). Differential scanning calorimetry, UV thermal denaturation, isothermal titration calorimetry and competition dialysis were used, together with computations of the hydrophobic free energy of binding, to determine the thermodynamic profile of MTA binding to DNA. The results were compared to those obtained in parallel using the structurally related mithramycin SK (MSK). The binding of MTA to salmon testes DNA determined by UV melting studies (K(obs) = 1.2 (+/-0.3) x 10(5) M(-1)) is tighter than that of MSK (2.9 (+/-1.0) x 10(4) M(-1)) at 25 degrees C. Competition dialysis studies showed a tighter MTA binding to both salmon testes DNA (42% C + G) and Micrococcus lysodeikticus DNA (72% C + G). The thermodynamic analysis of binding data at 25 degrees C shows that the binding of MTA and MSK to DNA is entropically driven, dominated by the hydrophobic transfer of the antibiotics from solution to the DNA-binding site. Direct molecular recognition between MTA or MSK and DNA through hydrogen bonding and van der Waals contacts may also contribute significantly to complex formation.

Published
2007
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