150 results on '"Agua-Doce A"'
Search Results
2. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study
- Author
-
Fendler, Annika, Shepherd, Scott T. C., Au, Lewis, Wilkinson, Katalin A., Wu, Mary, Byrne, Fiona, Cerrone, Maddalena, Schmitt, Andreas M., Joharatnam-Hogan, Nalinie, Shum, Benjamin, Tippu, Zayd, Rzeniewicz, Karolina, Boos, Laura Amanda, Harvey, Ruth, Carlyle, Eleanor, Edmonds, Kim, Del Rosario, Lyra, Sarker, Sarah, Lingard, Karla, Mangwende, Mary, Holt, Lucy, Ahmod, Hamid, Korteweg, Justine, Foley, Tara, Bazin, Jessica, Gordon, William, Barber, Taja, Emslie-Henry, Andrea, Xie, Wenyi, Gerard, Camille L., Deng, Daqi, Wall, Emma C., Agua-Doce, Ana, Namjou, Sina, Caidan, Simon, Gavrielides, Mike, MacRae, James I., Kelly, Gavin, Peat, Kema, Kelly, Denise, Murra, Aida, Kelly, Kayleigh, O’Flaherty, Molly, Dowdie, Lauren, Ash, Natalie, Gronthoud, Firza, Shea, Robyn L., Gardner, Gail, Murray, Darren, Kinnaird, Fiona, Cui, Wanyuan, Pascual, Javier, Rodney, Simon, Mencel, Justin, Curtis, Olivia, Stephenson, Clemency, Robinson, Anna, Oza, Bhavna, Farag, Sheima, Leslie, Isla, Rogiers, Aljosja, Iyengar, Sunil, Ethell, Mark, Messiou, Christina, Cunningham, David, Chau, Ian, Starling, Naureen, Turner, Nicholas, Welsh, Liam, van As, Nicholas, Jones, Robin L., Droney, Joanne, Banerjee, Susana, Tatham, Kate C., O’Brien, Mary, Harrington, Kevin, Bhide, Shreerang, Okines, Alicia, Reid, Alison, Young, Kate, Furness, Andrew J. S., Pickering, Lisa, Swanton, Charles, Gandhi, Sonia, Gamblin, Steve, Bauer, David L. V., Kassiotis, George, Kumar, Sacheen, Yousaf, Nadia, Jhanji, Shaman, Nicholson, Emma, Howell, Michael, Walker, Susanna, Wilkinson, Robert J., Larkin, James, and Turajlic, Samra
- Published
- 2021
- Full Text
- View/download PDF
3. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study
- Author
-
Fendler, Annika, Au, Lewis, Shepherd, Scott T. C., Byrne, Fiona, Cerrone, Maddalena, Boos, Laura Amanda, Rzeniewicz, Karolina, Gordon, William, Shum, Benjamin, Gerard, Camille L., Ward, Barry, Xie, Wenyi, Schmitt, Andreas M., Joharatnam-Hogan, Nalinie, Cornish, Georgina H., Pule, Martin, Mekkaoui, Leila, Ng, Kevin W., Carlyle, Eleanor, Edmonds, Kim, Rosario, Lyra Del, Sarker, Sarah, Lingard, Karla, Mangwende, Mary, Holt, Lucy, Ahmod, Hamid, Stone, Richard, Gomes, Camila, Flynn, Helen R., Agua-Doce, Ana, Hobson, Philip, Caidan, Simon, Howell, Michael, Wu, Mary, Goldstone, Robert, Crawford, Margaret, Cubitt, Laura, Patel, Harshil, Gavrielides, Mike, Nye, Emma, Snijders, Ambrosius P., MacRae, James I., Nicod, Jerome, Gronthoud, Firza, Shea, Robyn L., Messiou, Christina, Cunningham, David, Chau, Ian, Starling, Naureen, Turner, Nicholas, Welsh, Liam, van As, Nicholas, Jones, Robin L., Droney, Joanne, Banerjee, Susana, Tatham, Kate C., Jhanji, Shaman, O’Brien, Mary, Curtis, Olivia, Harrington, Kevin, Bhide, Shreerang, Bazin, Jessica, Robinson, Anna, Stephenson, Clemency, Slattery, Tim, Khan, Yasir, Tippu, Zayd, Leslie, Isla, Gennatas, Spyridon, Okines, Alicia, Reid, Alison, Young, Kate, Furness, Andrew J. S., Pickering, Lisa, Gandhi, Sonia, Gamblin, Steve, Swanton, Charles, Nicholson, Emma, Kumar, Sacheen, Yousaf, Nadia, Wilkinson, Katalin A., Swerdlow, Anthony, Harvey, Ruth, Kassiotis, George, Larkin, James, Wilkinson, Robert J., and Turajlic, Samra
- Published
- 2021
- Full Text
- View/download PDF
4. Umbilical cord tissue–derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing
- Author
-
Bárcia, Rita N., Santos, Jorge M., Teixeira, Mariana, Filipe, Mariana, Pereira, Ana Rita S., Ministro, Augusto, Água-Doce, Ana, Carvalheiro, Manuela, Gaspar, Maria Manuela, Miranda, Joana P., Graça, Luis, Simões, Sandra, Santos, Susana Constantino Rosa, Cruz, Pedro, and Cruz, Helder
- Published
- 2017
- Full Text
- View/download PDF
5. Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes
- Author
-
Tut, G, Lancaster, T, Krutikov, M, Sylla, P, Bone, D, Spalkova, E, Bentley, C, Amin, U, Jadir, A, Hulme, S, Kaur, N, Tut, E, Bruton, R, Wu, MY, Harvey, R, Carr, EJ, Clayton, B, Namjou, S, Silva, V, Poulten, M, Bawumia, P, Miah, M, Sade, S, Miranda, M, Taylor, T, D'angelo, I, Jarana, M Cabrera, Rahman, M, Abreu, J, Sandhar, S, Bailey, N, Caidan, S, Caulfield, M, Wu, M, Adams, L, Kavanagh, C, Warchal, S, Sawyer, C, Gavrielides, M, Kandasamy, J, Ambrose, K, Strange, A, Abiola, T, O'Reilly, N, Hobson, P, Agua-Doce, A, Russell, E, Riddell, A, Kjaer, S, Borg, A, Roustan, C, Queval, C, Ulferts, R, Swanton, C, Gandhi, S, Gamblin, S, Beale, R, Stirrup, O, Shrotri, M, Azmi, B, Fuller, C, Baynton, V, Irwin-Singer, A, Hayward, A, Copas, A, Shallcross, L, and Moss, P
- Subjects
Model organisms ,Chemical Biology & High Throughput ,Human Biology & Physiology ,FOS: Clinical medicine ,Stem Cells ,Genome Integrity & Repair ,Immunology ,Neurosciences ,Infectious Disease ,Cell Biology ,Tumour Biology ,Imaging ,Metabolism ,Ecology,Evolution & Ethology ,Cell Cycle & Chromosomes ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21–78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.
- Published
- 2023
- Full Text
- View/download PDF
6. Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation
- Author
-
Ribeiro, Filipa, Romão, Vasco C., Rosa, Sara, Jesus, Kátia, Agua-Doce, Ana, Barreira, Sofia, Martins, Patrícia, Silva, Susana, Nobre, Ema, Bugalho, Maria João, Fonseca, Valter R, Fonseca, João Eurico, Graca, Luis, and Repositório da Universidade de Lisboa
- Subjects
Multidisciplinary ,Programmed Cell Death 1 Receptor ,Humans ,Lupus Erythematosus, Systemic ,T-Lymphocytes, Helper-Inducer ,Hashimoto Disease ,T-Lymphocytes, Regulatory ,Autoantibodies - Abstract
© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto's thyroiditis (HT, n = 18), rheumatoid arthritis (RA, n = 16), or systemic lupus erythematosus (SLE, n = 32), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells (p = 0.0215) and a reduced Tfr/Tfh ratio (p = 0.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh (p = 0.0494 and p = 0.0392, respectively) and Tfr (p = 0.0003 and p = 0.0001, respectively) cells, resulting in an unchanged Tfr/Tfh ratio. Activated PD-1+ICOS+Tfh and CD4+PD-1+CXCR5-Tph cells were raised only in patients with SLE (p = 0.0022 and p = 0.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification., This work was supported by the Fundação para a Ciência e Tecnologia, Portugal (EJPRD/0003/2019).
- Published
- 2022
7. Adjuvant facilitates tolerance induction to factor VIII in hemophilic mice through a Foxp3-independent mechanism that relies on IL-10
- Author
-
Oliveira, Vanessa G., Agua-Doce, Ana, Curotto de Lafaille, Maria A., Lafaille, Juan J., and Graca, Luis
- Published
- 2013
- Full Text
- View/download PDF
8. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans
- Author
-
Dhira Joshi, Lucy R. Marshall, Lucy R. Wedderburn, Stavroula Paraskevopoulou, Steve Gamblin, Georgina H. Cornish, Sonia Gandhi, Charles Swanton, John W. McCauley, William Bolland, Svend Kjaer, Nikhil Faulkner, Hannah Rickman, Rachel Ulferts, Philip Hobson, D.J. Benton, Laura E. McCoy, Ana Agua-Doce, Rupert Beale, Annachiara Rosa, Chloe Roustan, Nicola O’Reilly, Catherine F Houlihan, Christopher Earl, Eleni Nastouli, A.G. Wrobel, Rachael Thompson, Brigitta Stockinger, Kirsty Thomson, Catherine Moore, Bethany R. Jebson, Anna Radziszewska, Coziana Ciurtin, Andrew Riddell, Saira Hussain, Emilie Sanchez, Peter Cherepanov, Elizabeth C. Rosser, Meredyth G. Ll Wilkinson, Kevin W. Ng, Ruth Harvey, Philip A. Walker, Hannah Peckham, Judith Heaney, Gee Yen Shin, Moira J. Spyer, and George Kassiotis
- Subjects
Male ,0301 basic medicine ,viruses ,Antibodies, Viral ,Viral Zoonoses ,Immunoglobulin G ,0302 clinical medicine ,030212 general & internal medicine ,skin and connective tissue diseases ,Aged, 80 and over ,chemistry.chemical_classification ,Multidisciplinary ,biology ,medicine.diagnostic_test ,virus diseases ,Microbio ,Middle Aged ,Multidisciplinary Sciences ,Titer ,Spike Glycoprotein, Coronavirus ,Science & Technology - Other Topics ,Female ,Antibody ,Adult ,General Science & Technology ,Immunology ,Flow cytometry ,Young Adult ,03 medical and health sciences ,Immunity ,Report ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Aged ,Science & Technology ,SARS-CoV-2 ,fungi ,COVID-19 ,biochemical phenomena, metabolism, and nutrition ,Immunity, Humoral ,Immunoglobulin A ,body regions ,HEK293 Cells ,030104 developmental biology ,Epitope mapping ,Immunoglobulin M ,chemistry ,Humoral immunity ,biology.protein ,Glycoprotein ,Epitope Mapping ,Reports - Abstract
Antibodies predating infection Immunological memory after infection with seasonal human coronaviruses (hCoVs) may potentially contribute to cross-protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ng et al. report that in a cohort of 350 SARS-CoV-2–uninfected individuals, a small proportion had circulating immunoglobulin G (IgG) antibodies that could cross-react with the S2 subunit of the SARS-CoV-2 spike protein (see the Perspective by Guthmiller and Wilson). By contrast, COVID-19 patients generated IgA, IgG, and IgM antibodies that recognized both the S1 and S2 subunits. The anti-S2 antibodies from SARS-CoV-2–uninfected patients showed specific neutralizing activity against both SARS-CoV-2 and SARS-CoV-2 S pseudotypes. A much higher percentage of SARS-CoV-2–uninfected children and adolescents were positive for these antibodies compared with adults. This pattern may be due to the fact that children and adolescents generally have higher hCoV infection rates and a more diverse antibody repertoire, which may explain the age distribution of COVID-19 susceptibility. Science, this issue p. 1339; see also p. 1272, SARS-CoV-2 neutralizing antibodies can be found in some uninfected individuals—predominantly children and adolescents., Zoonotic introduction of novel coronaviruses may encounter preexisting immunity in humans. Using diverse assays for antibodies recognizing SARS-CoV-2 proteins, we detected preexisting humoral immunity. SARS-CoV-2 spike glycoprotein (S)–reactive antibodies were detectable using a flow cytometry–based method in SARS-CoV-2–uninfected individuals and were particularly prevalent in children and adolescents. They were predominantly of the immunoglobulin G (IgG) class and targeted the S2 subunit. By contrast, SARS-CoV-2 infection induced higher titers of SARS-CoV-2 S–reactive IgG antibodies targeting both the S1 and S2 subunits, and concomitant IgM and IgA antibodies, lasting throughout the observation period. SARS-CoV-2–uninfected donor sera exhibited specific neutralizing activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes. Distinguishing preexisting and de novo immunity will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
- Published
- 2020
9. T follicular regulatory cells in mice and men
- Author
-
Maceiras, Ana Raquel, Fonseca, Valter R., Agua‐Doce, Ana, and Graca, Luis
- Published
- 2017
- Full Text
- View/download PDF
10. Contributors
- Author
-
Agua-Doce, A., primary, Awe, O., additional, Azevedo, R.I., additional, Bacchetta, R., additional, Bortell, R., additional, Brehm, M.A., additional, Burska, A.N., additional, Csomos, K., additional, Denny, J.C., additional, Dudley, J.T., additional, Farmer, J., additional, Getts, D.R., additional, Graca, L., additional, Greiner, D.L., additional, Harrison, S.R., additional, Hillion, S., additional, Kaplan, M.H., additional, Kidd, B.A., additional, Lacerda, J.F., additional, Lee, Y.N., additional, Miller, S.D., additional, Monteiro, M., additional, Ponchel, F., additional, Shultz, L.D., additional, Simon, Q., additional, Smarr, C.B., additional, Ueno, H., additional, Verma, M., additional, Walter, J.E., additional, Warner, J.L., additional, and Yang, Jianfei, additional
- Published
- 2016
- Full Text
- View/download PDF
11. Regulatory T Cells
- Author
-
Monteiro, M., primary, Agua-Doce, A., additional, Azevedo, R.I., additional, Lacerda, J.F., additional, and Graca, L., additional
- Published
- 2016
- Full Text
- View/download PDF
12. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study
- Author
-
Fendler, Annika, Shepherd, Scott TC, Au, Lewis, Wilkinson, Katalin A, Wu, Mary, Byrne, Fiona, Cerrone, Maddalena, Schmitt, Andreas M, Joharatnam-Hogan, Nalinie, Shum, Benjamin, Tippu, Zayd, Rzeniewicz, Karolina, Boos, Laura Amanda, Harvey, Ruth, Carlyle, Eleanor, Edmonds, Kim, Del Rosario, Lyra, Sarker, Sarah, Lingard, Karla, Mangwende, Mary, Holt, Lucy, Ahmod, Hamid, Korteweg, Justine, Foley, Tara, Bazin, Jessica, Gordon, William, Barber, Taja, Emslie-Henry, Andrea, Xie, Wenyi, Gerard, Camille L, Deng, Daqi, Wall, Emma C, Agua-Doce, Ana, Namjou, Sina, Caidan, Simon, Gavrielides, Mike, MacRae, James I, Kelly, Gavin, Peat, Kema, Kelly, Denise, Murra, Aida, Kelly, Kayleigh, O���Flaherty, Molly, Dowdie, Lauren, Ash, Natalie, Gronthoud, Firza, Shea, Robyn L, Gardner, Gail, Murray, Darren, Kinnaird, Fiona, Cui, Wanyuan, Pascual, Javier, Rodney, Simon, Mencel, Justin, Curtis, Olivia, Stephenson, Clemency, Robinson, Anna, Oza, Bhavna, Farag, Sheima, Leslie, Isla, Rogiers, Aljosja, Iyengar, Sunil, Ethell, Mark, Messiou, Christina, Cunningham, David, Chau, Ian, Starling, Naureen, Turner, Nicholas, Welsh, Liam, van As, Nicholas, Jones, Robin L, Droney, Joanne, Banerjee, Susana, Tatham, Kate C, O���Brien, Mary, Harrington, Kevin, Bhide, Shreerang, Okines, Alicia, Reid, Alison, Young, Kate, Furness, Andrew JS, Pickering, Lisa, Swanton, Charles, Consortium, The Crick COVID-19, Gandhi, Sonia, Gamblin, Steve, Bauer, David LV, Kassiotis, George, Kumar, Sacheen, Yousaf, Nadia, Jhanji, Shaman, Nicholson, Emma, Howell, Michael, Walker, Susanna, Wilkinson, Robert J, Larkin, James, Turajlic, Samra, and Consortium, The CAPTURE
- Subjects
Model organisms ,Chemical Biology & High Throughput ,Human Biology & Physiology ,FOS: Clinical medicine ,Stem Cells ,Genome Integrity & Repair ,Immunology ,Neurosciences ,Infectious Disease ,Cell Biology ,Tumour Biology ,Biochemistry & Proteomics ,Signalling & Oncogenes ,Metabolism ,Ecology,Evolution & Ethology ,Cell Cycle & Chromosomes ,Genetics & Genomics ,Developmental Biology ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.
- Published
- 2022
- Full Text
- View/download PDF
13. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study
- Author
-
Fendler, Annika, Au, Lewis, Shepherd, Scott TC, Byrne, Fiona, Cerrone, Maddalena, Boos, Laura Amanda, Rzeniewicz, Karolina, Gordon, William, Shum, Benjamin, Gerard, Camille L, Ward, Barry, Xie, Wenyi, Schmitt, Andreas M, Joharatnam-Hogan, Nalinie, Cornish, Georgina H, Pule, Martin, Mekkaoui, Leila, Ng, Kevin W, Carlyle, Eleanor, Edmonds, Kim, Del Rosario, Lyra, Sarker, Sarah, Lingard, Karla, Mangwende, Mary, Holt, Lucy, Ahmod, Hamid, Stone, Richard, Gomes, Camila, Flynn, Helen R, Agua-Doce, Ana, Hobson, Philip, Caidan, Simon, Howell, Michael, Wu, Mary, Goldstone, Robert, Crawford, Margaret, Cubitt, Laura, Patel, Harshil, Gavrielides, Mike, Nye, Emma, Snijders, Ambrosius P, MacRae, James I, Nicod, Jerome, Gronthoud, Firza, Shea, Robyn L, Messiou, Christina, Cunningham, David, Chau, Ian, Starling, Naureen, Turner, Nicholas, Welsh, Liam, van As, Nicholas, Jones, Robin L, Droney, Joanne, Banerjee, Susana, Tatham, Kate C, Jhanji, Shaman, O���Brien, Mary, Curtis, Olivia, Harrington, Kevin, Bhide, Shreerang, Bazin, Jessica, Robinson, Anna, Stephenson, Clemency, Slattery, Tim, Khan, Yasir, Tippu, Zayd, Leslie, Isla, Gennatas, Spyridon, Okines, Alicia, Reid, Alison, Young, Kate, Furness, Andrew JS, Pickering, Lisa, Gandhi, Sonia, Gamblin, Steve, Swanton, Charles, Consortium, The Crick COVID-19, Nicholson, Emma, Kumar, Sacheen, Yousaf, Nadia, Wilkinson, Katalin A, Swerdlow, Anthony, Harvey, Ruth, Kassiotis, George, Larkin, James, Wilkinson, Robert J, Turajlic, Samra, and consortium, The CAPTURE
- Subjects
Model organisms ,Chemical Biology & High Throughput ,Human Biology & Physiology ,FOS: Clinical medicine ,Stem Cells ,Genome Integrity & Repair ,Immunology ,Neurosciences ,Infectious Disease ,Cell Biology ,Tumour Biology ,Biochemistry & Proteomics ,Signalling & Oncogenes ,Metabolism ,Ecology,Evolution & Ethology ,Cell Cycle & Chromosomes ,Genetics & Genomics ,Developmental Biology ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.
- Published
- 2022
- Full Text
- View/download PDF
14. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study
- Author
-
Lisa Pickering, Richard Stone, Ian Chau, James I. MacRae, Karla Lingard, Susana Banerjee, Barry Ward, Jessica Bazin, William Gordon, Naureen Starling, Katalin A. Wilkinson, Mary O'Brien, Anna Robinson, Joanne Droney, Sacheen Kumar, Emma Nicholson, Martin Pule, Isla Leslie, Andreas M. Schmitt, Ambrosius P. Snijders, Karolina Rzeniewicz, Emma Nye, Benjamin Shum, Mary Mangwende, Scott Shepherd, Nalinie Joharatnam-Hogan, Robyn L. Shea, Michael Howell, Anthony J. Swerdlow, Shaman Jhanji, Simon Caidan, Eleanor Carlyle, Laura Amanda Boos, Annika Fendler, Kevin W. Ng, Kate Tatham, Leila Mekkaoui, Tim Slattery, Margaret Crawford, Firza Gronthoud, Philip Hobson, Camila Gomes, Robert J. Wilkinson, Jerome Nicod, Charles Swanton, Mike Gavrielides, Kim Edmonds, Robin L. Jones, Fiona Byrne, Laura Cubitt, Alison Reid, Lucy Holt, Ana Agua-Doce, Ruth Harvey, Sarah Sarker, Spyridon Gennatas, Camille L. Gerard, Andrew Furness, Hamid Ahmod, Liam Welsh, Nicholas van As, Olivia Curtis, Nadia Yousaf, Mary Wu, Nicholas C. Turner, Christina Messiou, David Cunningham, Zayd Tippu, Georgina H. Cornish, Sonia Gandhi, Helen R. Flynn, Harshil Patel, Yasir Khan, James Larkin, Lewis Au, George Kassiotis, Samra Turajlic, Maddalena Cerrone, Clemency Stephenson, Steve Gamblin, Kate Young, Wenyi Xie, Shreerang Bhide, Robert L. Goldstone, Alicia Okines, Kevin J. Harrington, Lyra Del Rosario, and Wellcome Trust
- Subjects
Cancer Research ,IMPACT ,Antibody Response ,Alpha (ethology) ,CORONAVIRUS DISEASE 2019 ,Disease ,Adaptive Immunity ,Article ,Immune system ,SEROCONVERSION ,Medicine ,Neutralizing antibody ,Cancer ,Science & Technology ,biology ,SARS-CoV-2 ,business.industry ,MORTALITY ,COVID-19 ,medicine.disease ,Titer ,SEVERITY ,Oncology ,Immunology ,Cohort ,biology.protein ,Prospective Study ,Antibody ,business ,Neutralising Antibodies ,Vaccine ,Life Sciences & Biomedicine ,T-cell Response - Abstract
Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.
- Published
- 2022
- Full Text
- View/download PDF
15. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study
- Author
-
Lisa Pickering, Nalinie Joharatnam-Hogan, Fiona Kinnaird, Andrew Furness, Mary Wu, Daqi Deng, Sina Namjou, Sarah Sarker, Aljosja Rogiers, Aida Murra, Justine Korteweg, Nicholas van As, Nicholas C. Turner, Anna Robinson, Joanne Droney, Kema Peat, Shaman Jhanji, Mike Gavrielides, Isla Leslie, Lauren Dowdie, Tara Foley, Christina Messiou, Natalie Ash, Taja Barber, Andrea Emslie-Henry, Simon Caidan, Karolina Rzeniewicz, Katalin A. Wilkinson, Ruth Harvey, Annika Fendler, Kate Tatham, Andreas M. Schmitt, Sunil Iyengar, Shreerang Bhide, Kayleigh Kelly, David L.V. Bauer, Benjamin Shum, Kim Edmonds, Gail Gardner, Scott Shepherd, Mark Ethell, Laura Amanda Boos, Liam Welsh, Robert J. Wilkinson, Lucy Holt, Alicia Okines, William Gordon, James I. MacRae, Maddalena Cerrone, Kevin J. Harrington, Mary Mangwende, Hamid Ahmod, Olivia Curtis, Emma Nicholson, Darren Murray, Susana Banerjee, Firza Gronthoud, Bhavna Oza, Naureen Starling, Wenyi Xie, Alison Reid, Karla Lingard, Ana Agua-Doce, Charles Swanton, Sacheen Kumar, Lewis Au, Michael Howell, James Larkin, Camille L. Gerard, Emma C Wall, Jessica Bazin, Ian Chau, Robin L. Jones, Fiona Byrne, Robyn L. Shea, Denise Kelly, Nadia Yousaf, Steve Gamblin, Kate Young, Sonia Gandhi, Susanna Walker, Eleanor Carlyle, Javier Pascual, David Cunningham, Samra Turajlic, Clemency Stephenson, Zayd Tippu, Gavin Kelly, Mary O'Brien, Sheima Farag, Molly O’Flaherty, George Kassiotis, Wanyuan Cui, Justin Mencel, Lyra Del Rosario, Simon Rodney, and Wellcome Trust
- Subjects
Male ,Cancer Research ,T-Lymphocytes ,Antibody Response ,Adaptive Immunity ,IMMUNOGENICITY ,Antibodies, Viral ,COVID-19 VACCINATION ,Immunogenicity, Vaccine ,Neoplasms ,Longitudinal Studies ,Prospective Studies ,Neutralizing antibody ,Prospective cohort study ,Cancer ,Aged, 80 and over ,Immunity, Cellular ,biology ,Vaccination ,Middle Aged ,Acquired immune system ,Kidney Neoplasms ,Oncology ,Female ,Antibody ,Life Sciences & Biomedicine ,Neutralising Antibodies ,T-cell Response ,Adult ,COVID-19 Vaccines ,Article ,MALIGNANCIES ,Crick COVID19 consortium ,Immunity ,VACCINES ,ChAdOx1 nCoV-19 ,medicine ,Humans ,Seroconversion ,Carcinoma, Renal Cell ,Pandemics ,BNT162 Vaccine ,Aged ,Science & Technology ,business.industry ,SARS-CoV-2 ,MORTALITY ,COVID-19 ,medicine.disease ,Antibodies, Neutralizing ,DEMOGRAPHICS ,Immunology ,biology.protein ,Prospective Study ,business ,Vaccine - Abstract
Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.
- Published
- 2021
16. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study
- Author
-
Fendler, Annika, primary, Shepherd, Scott, additional, Au, Lewis, additional, Wilkinson, Katalin, additional, Wu, Mary, additional, Byrne, Fiona, additional, Cerrone, Maddalena, additional, Schmitt, Andreas, additional, Joharatnam-Hogan, Nalinie, additional, Shum, Ben, additional, Tippu, Zayd, additional, Rzeniewicz, Karolina, additional, Boos, Laura, additional, Harvey, Ruth, additional, Carlyle, Eleanor, additional, Edmonds, Kim, additional, Rosario, Lyra Del, additional, Sarker, Sarah, additional, Lingard, Karla, additional, Mangwende, Mary, additional, Holt, Lucy, additional, Ahmod, Hamid, additional, Koreweg, Justine, additional, Foley, Tara, additional, Bazin, Jessica, additional, Gordon, William, additional, Barber, Taja, additional, Emslie-Henry, Andrea, additional, Xie, Wenyi, additional, Gerard, Camille, additional, Deng, Daqi, additional, Wall, Emma, additional, Agua-Doce, Ana, additional, Namjou, Sina, additional, Caidan, Simon, additional, Gavrielides, Mike, additional, MacRae, James, additional, Kelly, Gavin, additional, Peat, Kema, additional, Kelly, Denise, additional, Murra, Aida, additional, Kelly, Kayleigh, additional, O'Flaherty, Molly, additional, Dowdie, Lauren, additional, Ash, Natalie, additional, Grounthoud, Firza, additional, Shea, Robyn, additional, Gardner, Gail, additional, Murray, Darren, additional, Kinnaird, Fiona, additional, Cui, Wanyuan, additional, Pascual, Javier, additional, Rodney, Simon, additional, Mencel, Justin, additional, Curtis, Olivia, additional, Stephenson, Clemency, additional, Robinson, Anna, additional, Oza, Bhavna, additional, Farag, Sheima, additional, Leslie, Isla, additional, Rogiers, Aljosja, additional, Lyengar, Sunil, additional, Ethell, Mark, additional, Messiou, Christina, additional, Cunningham, David, additional, Chau, Ian, additional, Starling, Naureen, additional, Turner, Nicholas, additional, Welsh, Liam, additional, As, Nicholas van, additional, Jones, Robin, additional, DRoney, Joanne, additional, Banerjee, Susana, additional, Tatham, Kate, additional, O'Brien, Mary, additional, Harrington, Kevin, additional, Bhide, Shreerang, additional, Okines, Alicia, additional, Reid, Alison, additional, Young, Kate, additional, Furness, Andrew, additional, Pickering, Lisa, additional, Swanton, Charles, additional, Gandhi, Sonia, additional, Gamblin, Steve, additional, Bauer, David, additional, Kassiotis, George, additional, Kumar, Sacheen, additional, Yousaf, Nadia, additional, Jhanji, Shaman, additional, Nicholson, Emma, additional, Howell, Michael, additional, Walker, Susanna, additional, Wilkinson, Robert, additional, Larkin, James, additional, and Turajlic, Samra, additional
- Published
- 2021
- Full Text
- View/download PDF
17. Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study
- Author
-
Fendler, Annika, primary, Au, Lewis, additional, Shepherd, Scott, additional, Byrne, Fiona, additional, Cerrone, Maddalena, additional, Boos, Laura, additional, Rzeniewicz, Karolina, additional, Gordon, William, additional, Shum, Ben, additional, Gerard, Camille, additional, Ward, Barry, additional, Xie, Wenyi, additional, Schmitt, Andreas, additional, Joharatnam-Hogan, Nalinie, additional, Cornish, Georgina, additional, Pule, Martin, additional, Mekkaoui, Leila, additional, Ng, Kevin, additional, Carlyle, Eleanor, additional, Edmonds, Kim, additional, Rosario, Lyra Del, additional, Sarker, Sarah, additional, Lingard, Karla, additional, Mangwende, Mary, additional, Holt, Lucy, additional, Ahmod, Hamid, additional, Stone, Richard, additional, Gomes, Camila, additional, Flynn, Helen, additional, Agua-Doce, Ana, additional, Hobson, Philip, additional, Caidan, Simon, additional, Howell, Michael, additional, Wu, Mary, additional, Goldstone, Robert, additional, Crawford, Margaret, additional, Cubitt, Laura, additional, Patel, Harshil, additional, Gavrielides, Mike, additional, Nye, Emma, additional, Snijders, Ambrosius, additional, MacRae, James, additional, Nicod, Jerome, additional, Gronthoud, Firza, additional, Shea, Robyn, additional, Messiou, Christina, additional, Cunningham, David, additional, Chau, Ian, additional, Starling, Naureen, additional, Turner, Nicholas, additional, Welsh, Liam, additional, As, Nicholas van, additional, Jones, Robin, additional, Droney, Joanne, additional, Banerjee, Susana, additional, Tatham, Kate, additional, Jhanji, Shaman, additional, O'Brien, Mary, additional, Curtis, Oliva, additional, Harrington, Kevin, additional, Bhide, Shreerang, additional, Bazin, Jessica, additional, Robinson, Anna, additional, Stephenson, Clemency, additional, Slattery, Tim, additional, Khan, Yasir, additional, Tippu, Zayd, additional, Leslie, Isla, additional, Gennatas, Spyridon, additional, Okines, Alicia, additional, Reid, Alison, additional, Young, Kate, additional, Furness, Andrew, additional, Pickering, Lisa, additional, Gandhi, Sonia, additional, Gamblin, Steve, additional, Swanton, Charles, additional, Nicholson, Emma, additional, Kumar, Sacheen, additional, Yousaf, Nadia, additional, Wilkinson, Katalin, additional, Swerdlow, Anthony, additional, Harvey, Ruth, additional, Kassiotis, George, additional, Larkin, James, additional, Wilkinson, Robert, additional, and Turajlic, Samra, additional
- Published
- 2021
- Full Text
- View/download PDF
18. Adaptive immunity to SARS-CoV-2 in cancer patients: The CAPTURE study
- Author
-
Nicholas van As, Bram Snijders, Scott Thomas Colville Shepherd, Steve Gamblin, Kate Young, Adrian Hayday, James Larkin, Ben Shum, Laura Amanda Boos, Phillip Hobson, Tim Slattery, Georgina H. Cornish, Ana Agua-Doce, Olivia Curtis, Joanne Droney, Mike Gavrielides, Alison Reid, Helen R. Flynn, Katalin A. Wilkinson, Anthony J. Swerdlow, James I. MacRae, Susana Banerjee, Lewis Au, Shreerang Bhide, Michael Howell, Martin Pule, Nicholas C. Turner, Robin L. Jones, Fiona Byrne, Spyridon Gennatas, Christina Messiou, Richard Stone, Liam Welsh, Yasir Khan, Zayd Tippu, Firza Gronthoud, Camilla Gomes, Ruth Harvey, Naureen Starling, Maddalena Cerrone, Sacheen Kumar, Wenyi Xie, Barry Ward, Alicia Okines, Kevin J. Harrington, George Kassiotis, Nadia Yousaf, Annika Fendler, Kevin W. Ng, Kate Tatham, Jerome Nicod, Emma Nye, Andrew Furness, Shaman Jhanji, Simon Caidan, David Cunningham, Leila Mekkaoui, Samra Turajlic, Charles Swanton, Camille L. Gerard, Robert L. Goldstone, Ian Chau, Jennifer Rusby, Emma Nicholson, Isla Leslie, Robert J. Wilkinson, Lisa Pickering, and Sonia Ghandi
- Subjects
Oncology ,medicine.medical_specialty ,education.field_of_study ,biology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Population ,Cancer ,Acquired immune system ,medicine.disease ,Vaccination ,Immune profiling ,Immune system ,Internal medicine ,medicine ,biology.protein ,Antibody ,business ,education - Abstract
SUMMARYThere is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer patients and inform risk-reduction strategies and preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. SARS-CoV-2-specific T-cell responses were detected, and CD4+T-cell responses correlated with S1 antibody levels. Patients with haematological malignancies had impaired but partially compensated immune responses. Overall, cancer stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in the cancer population.
- Published
- 2020
19. Adapting to the Coronavirus Pandemic: Building and Incorporating a Diagnostic Pipeline in a Shared Resource Laboratory
- Author
-
Emma Russell, Dina Levi, Andrew Riddell, Philip Hobson, Ana Agua-Doce, Lotte Carr, Sukhveer Purewal, Hefin Rhys, Carl Henderson, Kerol Bartolovic, Debipriya Das, and Asha Malla
- Subjects
0301 basic medicine ,SRL ,Service (systems architecture) ,Histology ,Computer science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Operating procedures ,Assay ,Enzyme-Linked Immunosorbent Assay ,Development ,clinical ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Pipeline ,SARs‐CoV‐2 ,Pandemic ,Adaptation, Psychological ,Validation ,Humans ,Receipt ,Covid‐19 ,SARS-CoV-2 ,Flow ,pandemic ,COVID-19 ,Reproducibility of Results ,Cell Biology ,Flow Cytometry ,Pipeline (software) ,testing ,Shared resource ,Pipeline transport ,Engineering management ,030104 developmental biology ,030220 oncology & carcinogenesis ,SRL Communication ,SRL Communications ,ELISA ,Laboratories ,Cytometry - Abstract
In March 2020, with lockdown due to the coronavirus pandemic underway, the Francis Crick Institute (the Crick) regeared its research laboratories into clinical testing facilities. Two pipelines were established, one for polymerase chain reaction and the other for Serology. This article discusses the Cricks Flow Cytometry Science Technology Platform (Flow STP) role in setting up the Serology pipeline. Pipeline here referring to the overarching processes in place to facilitate the receipt of human sera through to a SARs‐CoV‐2 enzyme‐linked immunosorbent assay result. We examine the challenges that had to be overcome by a research laboratory to incorporate clinical diagnostics and the processes by which this was achieved. It describes the governance required to run the service, the design of the standard operating procedures (SOPs) and pipeline, the setting up of the assay, the validation required to show the robustness of the pipeline and reporting the results of the assay. Finally, as the lockdown started to ease in June 2020, it examines how this new service affects the daily running of the Flow STP. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.
- Published
- 2020
- Full Text
- View/download PDF
20. The fate of CD4+ T cells under tolerance-inducing stimulation: a modeling perspective
- Author
-
Caridade, Marta, Oliveira, Vanessa G, Agua-Doce, Ana, Graca, Luis, and Ribeiro, Ruy M
- Published
- 2013
- Full Text
- View/download PDF
21. Developmental bifurcation of human T follicular regulatory cells
- Author
-
Margarida Gama-Carvalho, F. N. Ribeiro, Saumya Kumar, Ana Agua-Doce, Tomás Gomes, Marta Monteiro, Ricardo J. Miragaia, Luis Graca, Eliane Piaggio, Elodie Segura, Sarah A. Teichmann, Afonso P. Basto, Válter R. Fonseca, and Dikélélé Elessa
- Subjects
0301 basic medicine ,Adult ,T cell ,Immunology ,Palatine Tonsil ,T-Lymphocytes, Regulatory ,Transcriptome ,Affinity maturation ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Follicular phase ,medicine ,Humans ,RNA-Seq ,Child ,biology ,Cell growth ,Germinal center ,Cell Differentiation ,General Medicine ,T-Lymphocytes, Helper-Inducer ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Lymph Nodes ,Antibody - Abstract
Germinal centers (GCs) are anatomic structures where B cells undergo affinity maturation, leading to production of high-affinity antibodies. The balance between T follicular helper (TFH) and regulatory (TFR) cells is critical for adequate control of GC responses. The study of human TFH and TFR cell development has been hampered because of the lack of in vitro assays reproducing in vivo biology, along with difficult access to healthy human lymphoid tissues. We used a single-cell transcriptomics approach to study the maturation of TFH and TFR cells isolated from human blood, iliac lymph nodes (LNs), and tonsils. As independent tissues have distinct proportions of follicular T cells in different maturation states, we leveraged the heterogeneity to reconstruct the maturation trajectory for human TFH and TFR cells. We found that the dominant maturation of TFR cells follows a bifurcated trajectory from precursor Treg cells, with one arm of the bifurcation leading to blood TFR cells and the other leading to the most mature GC TFR cells. Overall, our data provide a comprehensive resource for the transcriptomics of different follicular T cell populations and their dynamic relationship across different tissues.
- Published
- 2020
22. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers
- Author
-
Catherine F Houlihan, Nina Vora, Thomas Byrne, Dan Lewer, Gavin Kelly, Judith Heaney, Sonia Gandhi, Moira J Spyer, Rupert Beale, Peter Cherepanov, David Moore, Richard Gilson, Steve Gamblin, George Kassiotis, Laura E McCoy, Charles Swanton, Andrew Hayward, Eleni Nastouli, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell, Souradeep Basu, Clare Beesley, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J Blackman, Dominique Bonnet, Faye Bowker, Malgorzata Broncel, Claire Brooks, Michael D Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby, Claudio Bussi, Simon Butterworth, Fiona Byrne, Richard Byrne, Simon Caidan, Joanna Campbell, Johnathan Canton, Ana Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Natalie Chandler, Qu Chen, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina Cobolli Gigli, Zena Collins, Sally Cottrell, Margaret Crawford, Laura Cubitt, Tom Cullup, Heledd Davies, Patrick Davis, Dara Davison, Annalisa D'Avola, Vicky Dearing, Solene Debaisieux, Monica Diaz-Romero, Alison Dibbs, Jessica Diring, Paul C Driscoll, Christopher Earl, Amelia Edwards, Chris Ekin, Dimitrios Evangelopoulos, Rupert Faraway, Antony Fearns, Aaron Ferron, Efthymios Fidanis, Dan Fitz, James Fleming, Bruno Frederico, Alessandra Gaiba, Anthony Gait, Liam Gaul, Helen M Golding, Jacki Goldman, Robert Goldstone, Belen Gomez Dominguez, Hui Gong, Paul R Grant, Maria Greco, Mariana Grobler, Anabel Guedan, Maximiliano G Gutierrez, Fiona Hackett, Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Lyn Healy, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Steve Hindmarsh, Rajnika Hirani, Joshua Hope, Elizabeth Horton, Beth Hoskins, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint R Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz Huseynova, Ming-Shih Hwang, Rachael Instrell, Deborah Jackson, Mariam Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Nnennaya Kanu, Louise Kiely, Anastacio King Spert Teixeira, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris, Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe, Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Hon-Wing Liu, Sam Loughlin, Wei-Ting Lu, James I MacRae, Akshay Madoo, Julie A Marczak, Mimmi Martensson, Thomas Martinez, Bishara Marzook, John Matthews, Joachim M Matz, Samuel McCall, Fiona McKay, Edel C McNamara, Carlos M Minutti, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie Montgomery, Catherine Moore, Anastasia Moraiti, Lucia Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Aileen Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Caroline Oedekoven, Anne O'Garra, Jean D O'Leary, Jessica Olsen, Olga O'Neill, Paula Ordonez Suarez, Nicola O'Reilly, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos Papayannopoulos, Namita Patel, Yogen Patel, Oana Paun, Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S Perrault, Abigail Perrin, Roy Poh, Enzo Z Poirier, James M Polke, Marc Pollitt, Lucia Prieto-Godino, Alize Proust, Rajvee Shah Punatar, Clinda Puvirajasinghe, Christophe Queval, Vijaya Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Laura Reed, Caetano Reis e Sousa, Kayleigh Richardson, Sophie Ridewood, Rowenna Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Theo Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Jill A Saunders, Chelsea Sawyer, Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Joe Shaw, Gee Yen Shin, Mariana Silva Dos Santos, Margaux Silvestre, Matthew Singer, Daniel M Snell, Ok-Ryul Song, Louisa Steel, Amy Strange, Adrienne E Sullivan, Michele SY Tan, Zoe H Tautz-Davis, Effie Taylor, Gunes Taylor, Harriet B Taylor, Alison Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Patrick Toolan-Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C Tsai, James MA Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P Vanloo, Selvaraju Veeriah, Subramanian Venkatesan, Karen Vousden, Andreas Wack, Claire Walder, Philip A Walker, Yiran Wang, Sophia Ward, Catharina Wenman, Luke Wiliams, Matthew J Williams, Wai Keong Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian A Zagalak, Davide Zecchin, Rachel Zillwood, Rebecca Matthews, Abigail Severn, Sajida Adam, Louise Enfield, Angela McBride, Kathleen Gärtner, Sarah Edwards, Fabiana Lorencatto, Susan Michie, Ed Manley, Maryam Shahmanesh, Hinal Lukha, Paulina Prymas, Hazel McBain, Robert Shortman, Leigh Wood, Claudia Davies, Bethany Williams, Kevin W Ng, Georgina H Cornish, Nikhil Faulkner, Andrew Riddell, Philip Hobson, Ana Agua-Doce, Kerol Bartolovic, Emma Russell, Lotte Carr, Emilie Sanchez, Daniel Frampton, Matthew Byott, Stavroula M Paraskevopoulou, Elise Crayton, Carly Meyer, Triantafylia Gkouleli, Andrea Stoltenberg, Veronica Ranieri, Tom Byrne, Fiona Roberts, and Emine Hatipoglu
- Subjects
Adult ,2019-20 coronavirus outbreak ,Infectious Disease Transmission, Patient-to-Professional ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Health Personnel ,Pneumonia, Viral ,Viral transmission ,Antibodies, Viral ,Risk Assessment ,Article ,Betacoronavirus ,Environmental health ,Occupational Exposure ,Pandemic ,Health care ,London ,Medicine ,Humans ,Prospective Studies ,Seroconversion ,Pandemics ,Cross Infection ,business.industry ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Occupational exposure ,business ,Coronavirus Infections - Published
- 2020
23. Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans
- Author
-
Kevin W. Ng, Nikhil Faulkner, Georgina H. Cornish, Annachiara Rosa, Ruth Harvey, Saira Hussain, Rachel Ulferts, Christopher Earl, Antoni Wrobel, Donald Benton, Chloe Roustan, William Bolland, Rachael Thompson, Ana Agua-Doce, Philip Hobson, Judith Heaney, Hannah Rickman, Stavroula Paraskevopoulou, Catherine F. Houlihan, Kirsty Thomson, Emilie Sanchez, David Brealey, Gee Yen Shin, Moira J. Spyer, Dhira Joshi, Nicola O’Reilly, Philip A. Walker, Svend Kjaer, Andrew Riddell, Catherine Moore, Bethany R. Jebson, Meredyth G.Ll. Wilkinson, Lucy R. Marshall, Elizabeth C. Rosser, Anna Radziszewska, Hannah Peckham, Coziana Ciurtin, Lucy R. Wedderburn, Rupert Beale, Charles Swanton, Sonia Gandhi, Brigitta Stockinger, John McCauley, Steve Gamblin, Laura E. McCoy, Peter Cherepanov, Eleni Nastouli, and George Kassiotis
- Subjects
chemistry.chemical_classification ,education.field_of_study ,Zoonotic Infection ,viruses ,fungi ,Population ,virus diseases ,Biology ,medicine.disease_cause ,Virology ,Nucleoprotein ,body regions ,chemistry ,Immunity ,Humoral immunity ,medicine ,biology.protein ,Antibody ,skin and connective tissue diseases ,education ,Glycoprotein ,Coronavirus - Abstract
Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections1. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions2,3. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 spike (S) glycoprotein, we demonstrate the presence of pre-existing humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry-based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2-uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS-CoV-2 will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection.
- Published
- 2020
24. The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome
- Author
-
Ana Agua-Doce, Válter R. Fonseca, Ana Cristina Ferreira, Dolores López-Presa, Luis Graca, Mara Santos, João Eurico Fonseca, and Vasco C. Romão
- Subjects
0301 basic medicine ,Salivary gland ,medicine.diagnostic_test ,business.industry ,T cell ,Immunology ,Cell ,medicine.disease ,Sialadenitis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Rheumatology ,Sicca syndrome ,Follicular phase ,Biopsy ,medicine ,Immunology and Allergy ,business ,B cell ,030215 immunology - Abstract
Objective To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjogren's syndrome (SS). Methods We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. Results Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. Conclusion The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
- Published
- 2018
25. Adaptive immunity to SARS-CoV-2 in cancer patients: The CAPTURE study
- Author
-
Fendler, Annika, primary, Au, Lewis, additional, Boos, Laura Amanda, additional, Byrne, Fiona, additional, Shepherd, Scott T.C., additional, Shum, Ben, additional, Gerard, Camille L., additional, Ward, Barry, additional, Xie, Wenyi, additional, Cerrone, Maddalena, additional, Cornish, Georgina H., additional, Pule, Martin, additional, Mekkaoui, Leila, additional, Ng, Kevin W., additional, Stone, Richard, additional, Gomes, Camila, additional, Flynn, Helen R., additional, Agua-Doce, Ana, additional, Hobson, Phillip, additional, Caidan, Simon, additional, Howell, Mike, additional, Goldstone, Robert, additional, Gavrielides, Mike, additional, Nye, Emma, additional, Snijders, Bram, additional, Macrae, James, additional, Nicod, Jerome, additional, Hayday, Adrian, additional, Gronthoud, Firza, additional, Messiou, Christina, additional, Cunningham, David, additional, Chau, Ian, additional, Starling, Naureen, additional, Turner, Nicholas, additional, Rusby, Jennifer, additional, Welsh, Liam, additional, van As, Nicholas, additional, Jones, Robin, additional, Droney, Joanne, additional, Banerjee, Susana, additional, Tatham, Kate, additional, Jhanji, Shaman, additional, O’Brien, Mary, additional, Curtis, Olivia, additional, Harrington, Kevin, additional, Bhide, Shreerang, additional, Slattery, Tim, additional, Khan, Yasir, additional, Tippu, Zayd, additional, Leslie, Isla, additional, Gennatas, Spyridon, additional, Okines, Alicia, additional, Reid, Alison, additional, Young, Kate, additional, Furness, Andrew, additional, Pickering, Lisa, additional, Ghandi, Sonia, additional, Gamblin, Steve, additional, Swanton, Charles, additional, Nicholson, Emma, additional, Kumar, Sacheen, additional, Yousaf, Nadia, additional, Wilkinson, Katalin, additional, Swerdlow, Anthony, additional, Harvey, Ruth, additional, Kassiotis, George, additional, Wilkinson, Robert, additional, Larkin, James, additional, and Turajlic, Samra, additional
- Published
- 2020
- Full Text
- View/download PDF
26. Preexisting and de novo humoral immunity to SARS-CoV-2 in humans
- Author
-
Ng, Kevin W., primary, Faulkner, Nikhil, additional, Cornish, Georgina H., additional, Rosa, Annachiara, additional, Harvey, Ruth, additional, Hussain, Saira, additional, Ulferts, Rachel, additional, Earl, Christopher, additional, Wrobel, Antoni G., additional, Benton, Donald J., additional, Roustan, Chloe, additional, Bolland, William, additional, Thompson, Rachael, additional, Agua-Doce, Ana, additional, Hobson, Philip, additional, Heaney, Judith, additional, Rickman, Hannah, additional, Paraskevopoulou, Stavroula, additional, Houlihan, Catherine F., additional, Thomson, Kirsty, additional, Sanchez, Emilie, additional, Shin, Gee Yen, additional, Spyer, Moira J., additional, Joshi, Dhira, additional, O’Reilly, Nicola, additional, Walker, Philip A., additional, Kjaer, Svend, additional, Riddell, Andrew, additional, Moore, Catherine, additional, Jebson, Bethany R., additional, Wilkinson, Meredyth, additional, Marshall, Lucy R., additional, Rosser, Elizabeth C., additional, Radziszewska, Anna, additional, Peckham, Hannah, additional, Ciurtin, Coziana, additional, Wedderburn, Lucy R., additional, Beale, Rupert, additional, Swanton, Charles, additional, Gandhi, Sonia, additional, Stockinger, Brigitta, additional, McCauley, John, additional, Gamblin, Steve J., additional, McCoy, Laura E., additional, Cherepanov, Peter, additional, Nastouli, Eleni, additional, and Kassiotis, George, additional
- Published
- 2020
- Full Text
- View/download PDF
27. Adapting to the Coronavirus Pandemic: Building and Incorporating a Diagnostic Pipeline in a Shared Resource Laboratory
- Author
-
Russell, Emma, primary, Agua‐Doce, Ana, additional, Carr, Lotte, additional, Malla, Asha, additional, Bartolovic, Kerol, additional, Levi, Dina, additional, Henderson, Carl, additional, Das, Debipriya, additional, Rhys, Hefin, additional, Hobson, Philip, additional, Purewal, Sukhveer, additional, and Riddell, Andrew, additional
- Published
- 2020
- Full Text
- View/download PDF
28. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers
- Author
-
Houlihan, Catherine F, primary, Vora, Nina, additional, Byrne, Thomas, additional, Lewer, Dan, additional, Kelly, Gavin, additional, Heaney, Judith, additional, Gandhi, Sonia, additional, Spyer, Moira J, additional, Beale, Rupert, additional, Cherepanov, Peter, additional, Moore, David, additional, Gilson, Richard, additional, Gamblin, Steve, additional, Kassiotis, George, additional, McCoy, Laura E, additional, Swanton, Charles, additional, Hayward, Andrew, additional, Nastouli, Eleni, additional, Aitken, Jim, additional, Allen, Zoe, additional, Ambler, Rachel, additional, Ambrose, Karen, additional, Ashton, Emma, additional, Avola, Alida, additional, Balakrishnan, Samutheswari, additional, Barns-Jenkins, Caitlin, additional, Barr, Genevieve, additional, Barrell, Sam, additional, Basu, Souradeep, additional, Beesley, Clare, additional, Bhardwaj, Nisha, additional, Bibi, Shahnaz, additional, Bineva-Todd, Ganka, additional, Biswas, Dhruva, additional, Blackman, Michael J, additional, Bonnet, Dominique, additional, Bowker, Faye, additional, Broncel, Malgorzata, additional, Brooks, Claire, additional, Buck, Michael D, additional, Buckton, Andrew, additional, Budd, Timothy, additional, Burrell, Alana, additional, Busby, Louise, additional, Bussi, Claudio, additional, Butterworth, Simon, additional, Byrne, Fiona, additional, Byrne, Richard, additional, Caidan, Simon, additional, Campbell, Joanna, additional, Canton, Johnathan, additional, Cardoso, Ana, additional, Carter, Nick, additional, Carvalho, Luiz, additional, Carzaniga, Raffaella, additional, Chandler, Natalie, additional, Chen, Qu, additional, Churchward, Laura, additional, Clark, Graham, additional, Clayton, Bobbi, additional, Cobolli Gigli, Clementina, additional, Collins, Zena, additional, Cottrell, Sally, additional, Crawford, Margaret, additional, Cubitt, Laura, additional, Cullup, Tom, additional, Davies, Heledd, additional, Davis, Patrick, additional, Davison, Dara, additional, D'Avola, Annalisa, additional, Dearing, Vicky, additional, Debaisieux, Solene, additional, Diaz-Romero, Monica, additional, Dibbs, Alison, additional, Diring, Jessica, additional, Driscoll, Paul C, additional, Earl, Christopher, additional, Edwards, Amelia, additional, Ekin, Chris, additional, Evangelopoulos, Dimitrios, additional, Faraway, Rupert, additional, Fearns, Antony, additional, Ferron, Aaron, additional, Fidanis, Efthymios, additional, Fitz, Dan, additional, Fleming, James, additional, Frederico, Bruno, additional, Gaiba, Alessandra, additional, Gait, Anthony, additional, Gaul, Liam, additional, Golding, Helen M, additional, Goldman, Jacki, additional, Goldstone, Robert, additional, Gomez Dominguez, Belen, additional, Gong, Hui, additional, Grant, Paul R, additional, Greco, Maria, additional, Grobler, Mariana, additional, Guedan, Anabel, additional, Gutierrez, Maximiliano G, additional, Hackett, Fiona, additional, Hall, Ross, additional, Halldorsson, Steinar, additional, Harris, Suzanne, additional, Hashim, Sugera, additional, Healy, Lyn, additional, Herbst, Susanne, additional, Hewitt, Graeme, additional, Higgins, Theresa, additional, Hindmarsh, Steve, additional, Hirani, Rajnika, additional, Hope, Joshua, additional, Horton, Elizabeth, additional, Hoskins, Beth, additional, Houlihan, Catherine F, additional, Howell, Michael, additional, Howitt, Louise, additional, Hoyle, Jacqueline, additional, Htun, Mint R, additional, Hubank, Michael, additional, Huerga Encabo, Hector, additional, Hughes, Deborah, additional, Hughes, Jane, additional, Huseynova, Almaz, additional, Hwang, Ming-Shih, additional, Instrell, Rachael, additional, Jackson, Deborah, additional, Jamal-Hanjani, Mariam, additional, Jenkins, Lucy, additional, Jiang, Ming, additional, Johnson, Mark, additional, Jones, Leigh, additional, Kanu, Nnennaya, additional, Kiely, Louise, additional, King Spert Teixeira, Anastacio, additional, Kirk, Stuart, additional, Kjaer, Svend, additional, Knuepfer, Ellen, additional, Komarov, Nikita, additional, Kotzampaltiris, Paul, additional, Kousis, Konstantinos, additional, Krylova, Tammy, additional, Kucharska, Ania, additional, Labrum, Robyn, additional, Lambe, Catherine, additional, Lappin, Michelle, additional, Lee, Stacey-Ann, additional, Levett, Andrew, additional, Levett, Lisa, additional, Levi, Marcel, additional, Liu, Hon-Wing, additional, Loughlin, Sam, additional, Lu, Wei-Ting, additional, MacRae, James I, additional, Madoo, Akshay, additional, Marczak, Julie A, additional, Martensson, Mimmi, additional, Martinez, Thomas, additional, Marzook, Bishara, additional, Matthews, John, additional, Matz, Joachim M, additional, McCall, Samuel, additional, McKay, Fiona, additional, McNamara, Edel C, additional, Minutti, Carlos M, additional, Mistry, Gita, additional, Molina-Arcas, Miriam, additional, Montaner, Beatriz, additional, Montgomery, Kylie, additional, Moore, Catherine, additional, Moraiti, Anastasia, additional, Moreira-Teixeira, Lucia, additional, Mukherjee, Joyita, additional, Naceur-Lombardelli, Cristina, additional, Nelson, Aileen, additional, Nicod, Jerome, additional, Nightingale, Luke, additional, Nofal, Stephanie, additional, Nurse, Paul, additional, Nutan, Savita, additional, Oedekoven, Caroline, additional, O'Garra, Anne, additional, O'Leary, Jean D, additional, Olsen, Jessica, additional, O'Neill, Olga, additional, Ordonez Suarez, Paula, additional, O'Reilly, Nicola, additional, Osborne, Neil, additional, Pabari, Amar, additional, Pajak, Aleksandra, additional, Papayannopoulos, Venizelos, additional, Patel, Namita, additional, Patel, Yogen, additional, Paun, Oana, additional, Peat, Nigel, additional, Peces-Barba Castano, Laura, additional, Perez Caballero, Ana, additional, Perez-Lloret, Jimena, additional, Perrault, Magali S, additional, Perrin, Abigail, additional, Poh, Roy, additional, Poirier, Enzo Z, additional, Polke, James M, additional, Pollitt, Marc, additional, Prieto-Godino, Lucia, additional, Proust, Alize, additional, Shah Punatar, Rajvee, additional, Puvirajasinghe, Clinda, additional, Queval, Christophe, additional, Ramachandran, Vijaya, additional, Ramaprasad, Abhinay, additional, Ratcliffe, Peter, additional, Reed, Laura, additional, Reis e Sousa, Caetano, additional, Richardson, Kayleigh, additional, Ridewood, Sophie, additional, Roberts, Rowenna, additional, Rodgers, Angela, additional, Romero Clavijo, Pablo, additional, Rosa, Annachiara, additional, Rossi, Alice, additional, Roustan, Chloe, additional, Rowan, Andrew, additional, Sahai, Erik, additional, Sait, Aaron, additional, Sala, Katarzyna, additional, Sanderson, Theo, additional, Santucci, Pierre, additional, Sardar, Fatima, additional, Sateriale, Adam, additional, Saunders, Jill A, additional, Sawyer, Chelsea, additional, Schlott, Anja, additional, Schweighoffer, Edina, additional, Segura-Bayona, Sandra, additional, Shaw, Joe, additional, Shin, Gee Yen, additional, Silva Dos Santos, Mariana, additional, Silvestre, Margaux, additional, Singer, Matthew, additional, Snell, Daniel M, additional, Song, Ok-Ryul, additional, Steel, Louisa, additional, Strange, Amy, additional, Sullivan, Adrienne E, additional, Tan, Michele SY, additional, Tautz-Davis, Zoe H, additional, Taylor, Effie, additional, Taylor, Gunes, additional, Taylor, Harriet B, additional, Taylor-Beadling, Alison, additional, Teixeira Subtil, Fernanda, additional, Terré Torras, Berta, additional, Toolan-Kerr, Patrick, additional, Torelli, Francesca, additional, Toteva, Tea, additional, Treeck, Moritz, additional, Trojer, Hadija, additional, Tsai, Ming-Han C, additional, Turner, James MA, additional, Turner, Melanie, additional, Ule, Jernej, additional, Ulferts, Rachel, additional, Vanloo, Sharon P, additional, Veeriah, Selvaraju, additional, Venkatesan, Subramanian, additional, Vousden, Karen, additional, Wack, Andreas, additional, Walder, Claire, additional, Walker, Philip A, additional, Wang, Yiran, additional, Ward, Sophia, additional, Wenman, Catharina, additional, Wiliams, Luke, additional, Williams, Matthew J, additional, Wong, Wai Keong, additional, Wright, Joshua, additional, Wu, Mary, additional, Wynne, Lauren, additional, Xiang, Zheng, additional, Yap, Melvyn, additional, Zagalak, Julian A, additional, Zecchin, Davide, additional, Zillwood, Rachel, additional, Matthews, Rebecca, additional, Severn, Abigail, additional, Adam, Sajida, additional, Enfield, Louise, additional, McBride, Angela, additional, Gärtner, Kathleen, additional, Edwards, Sarah, additional, Lorencatto, Fabiana, additional, Michie, Susan, additional, Manley, Ed, additional, Shahmanesh, Maryam, additional, Lukha, Hinal, additional, Prymas, Paulina, additional, McBain, Hazel, additional, Shortman, Robert, additional, Wood, Leigh, additional, Davies, Claudia, additional, Williams, Bethany, additional, Ng, Kevin W, additional, Cornish, Georgina H, additional, Faulkner, Nikhil, additional, Riddell, Andrew, additional, Hobson, Philip, additional, Agua-Doce, Ana, additional, Bartolovic, Kerol, additional, Russell, Emma, additional, Carr, Lotte, additional, Sanchez, Emilie, additional, Frampton, Daniel, additional, Byott, Matthew, additional, Paraskevopoulou, Stavroula M, additional, Crayton, Elise, additional, Meyer, Carly, additional, Gkouleli, Triantafylia, additional, Stoltenberg, Andrea, additional, Ranieri, Veronica, additional, Byrne, Tom, additional, Roberts, Fiona, additional, and Hatipoglu, Emine, additional
- Published
- 2020
- Full Text
- View/download PDF
29. Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans
- Author
-
Ng, Kevin W., primary, Faulkner, Nikhil, additional, Cornish, Georgina H., additional, Rosa, Annachiara, additional, Harvey, Ruth, additional, Hussain, Saira, additional, Ulferts, Rachel, additional, Earl, Christopher, additional, Wrobel, Antoni, additional, Benton, Donald, additional, Roustan, Chloe, additional, Bolland, William, additional, Thompson, Rachael, additional, Agua-Doce, Ana, additional, Hobson, Philip, additional, Heaney, Judith, additional, Rickman, Hannah, additional, Paraskevopoulou, Stavroula, additional, Houlihan, Catherine F., additional, Thomson, Kirsty, additional, Sanchez, Emilie, additional, Brealey, David, additional, Shin, Gee Yen, additional, Spyer, Moira J., additional, Joshi, Dhira, additional, O’Reilly, Nicola, additional, Walker, Philip A., additional, Kjaer, Svend, additional, Riddell, Andrew, additional, Moore, Catherine, additional, Jebson, Bethany R., additional, Wilkinson, Meredyth G.Ll., additional, Marshall, Lucy R., additional, Rosser, Elizabeth C., additional, Radziszewska, Anna, additional, Peckham, Hannah, additional, Ciurtin, Coziana, additional, Wedderburn, Lucy R., additional, Beale, Rupert, additional, Swanton, Charles, additional, Gandhi, Sonia, additional, Stockinger, Brigitta, additional, McCauley, John, additional, Gamblin, Steve, additional, McCoy, Laura E., additional, Cherepanov, Peter, additional, Nastouli, Eleni, additional, and Kassiotis, George, additional
- Published
- 2020
- Full Text
- View/download PDF
30. T follicular regulatory cells in mice and men
- Author
-
Ana Raquel Maceiras, Ana Agua-Doce, Luis Graca, and Válter R. Fonseca
- Subjects
0301 basic medicine ,Immunology ,Autoimmunity ,Thymus Gland ,T-Lymphocytes, Regulatory ,Mice ,03 medical and health sciences ,Interleukin 21 ,0302 clinical medicine ,T-Lymphocyte Subsets ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,Review Articles ,Autoantibodies ,CD40 ,biology ,ZAP70 ,Germinal center ,Germinal Center ,Natural killer T cell ,Cell biology ,Phenotype ,030104 developmental biology ,Immune System Diseases ,biology.protein ,Cytokines ,Biomarkers ,030215 immunology - Abstract
It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal centre (GC) reaction where affinity maturation and isotype switching occur. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T-cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously presenting characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression). These Tfr cells have been implicated in the regulation of the magnitude of the GC reaction, as well as in protection from immune-mediated pathology.
- Published
- 2017
31. T Follicular Regulatory Cells Are Decreased in Patients With Established Treated Rheumatoid Arthritis With Active Disease: Comment on the Article by Liu et al
- Author
-
João Eurico Fonseca, Vasco C. Romão, Luis Graca, and Ana Agua-Doce
- Subjects
030203 arthritis & rheumatology ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,medicine.disease ,T-Lymphocytes, Regulatory ,Arthritis, Rheumatoid ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Text mining ,Rheumatology ,Rheumatoid arthritis ,Internal medicine ,Follicular phase ,Active disease ,Humans ,Immunology and Allergy ,Medicine ,In patient ,business ,Medical science ,Autoantibodies - Published
- 2018
32. THU0045 Expansion of activated cxcr5+icos+ tfh cells and plasmablasts induced by seasonal influenza vaccine is impaired in anti-il-6r treated rheumatoid arthritis patients
- Author
-
J. E. Fonseca, Luis Graca, Rubens Pessoa de Barros, Vasco C. Romão, Ana Agua-Doce, M.I. Seixas, Joaquim Polido-Pereira, E. Sacadura-Leite, Inês P Lopes, H. Rebelo-de-Andrade, and Maria José Saavedra
- Subjects
biology ,business.industry ,Interleukin ,FOXP3 ,CD38 ,CXCR3 ,Immunoglobulin D ,CD19 ,medicine.anatomical_structure ,Immunology ,biology.protein ,Medicine ,IL-2 receptor ,business ,B cell - Abstract
Background T follicular helper (Tfh) cells are essential for the generation of high affinity neutralising antibodies elicited following vaccination and are involved in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)−6 has been shown to be critical for Tfh differentiation in mice, while its importance in humans has been less clear, given the lack of adequate in vivo assessment. Objectives To investigate the importance of IL-6 for the in vivo differentiation of human Tfh cells, taking advantage of influenza vaccination in patients under anti-IL-6R therapy. Methods Blood was collected before, 7 and 28 days after vaccination from established RA patients treated with tocilizumab (TCZ, IL-6R blocker), methotrexate (MTX) ±other DMARDs and age- and sex-matched healthy donors (HD). We analysed the frequency of Tfh (CD3+CD4+CD25-Foxp3-CXCR5+CD45RO+), T follicular regulatory (Tfr, CD3+CD4+CD25+Foxp3+CXCR5+) and B cell populations at each time point. We used non-parametric tests, deemed significant at p Results We included 137 participants (42 TCZ, 42 MTX, 53 HD) with similar age and gender distribution. Patients from the TCZ group had more active and severe disease. At baseline, patients treated with TCZ had higher frequency of Tfh and Tfh-Th2-like cells (CXCR3-CCR6-) and lower frequency of Tfr-Th1-like (CXCR3+CCR6-) and B cells. Following influenza vaccination, the overall blood Tfh and Tfr populations remained unchanged in all groups. However, as previously reported, there were marked changes in specific subsets at day 7 of HD following vaccination. We found a marked expansion of activated CXCR5+ICOS+ Tfh cells at day 7, in HD and MTX-treated patients, but this was impaired in the TCZ group (figure 1). The increase in activated CXCR5+ICOS+ Tfh cells was mainly due to a Tfh-Th1-like subpopulation, greatly increased in HD and MTX-treated patients (figure 1). Of note, CXCR5+ICOS+ Tfh-Th17-like cells also accumulated in HD but not in RA patients. The proliferative capacity of CXCR5+ICOS+ Tfh cells seemed to be partially impaired in patients under IL-6R blockade, that displayed marked reduction of Ki67+CD38+ proliferative cells within that compartment (figure 1). Anti-IL-6R treatment also impaired expansion of CD19+IgD- CD27+CD38hi plasmablasts following vaccination, when compared with both MTX and HD groups (figure 1). Changes in CXCR5+ICOS+ Tfh and plasmablasts were significantly correlated in all groups. Conclusions Anti-IL-6R treatment limits proliferative ability of activated CXCR5+ICOS+ Tfh cells, blocking their emergence as well as plasmablast accumulation following influenza vaccination. Our data suggest that IL-6 is crucial for optimal in vivo generation of activated Tfh cells in humans. Disclosure of Interest None declared
- Published
- 2018
33. Expansion of activated cxcr5+icos+ tfh cells and plasmablasts induced by seasonal influenza vaccine is impaired in anti-il-6r treated rheumatoid arthritis patients
- Author
-
Romao, V.C., Agua-Doce, A., Polido-Pereira, J., Barros, R., Lopes, I.P., Seixas, M.I., Saavedra, M.J., Sacadura-Leite, E., Rebelo-de-Andrade, H., Fonseca, J.E., and Graca, L.
- Subjects
Infecções Respiratórias ,Influenza Vaccination ,Influenza Vaccine ,Influenza - Abstract
Objectives: To investigate the importance of IL-6 for the in vivo differentiation of human Tfh cells, taking advantage of influenza vaccination in patients under anti-IL-6R therapy. info:eu-repo/semantics/publishedVersion
- Published
- 2018
34. Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance
- Author
-
Juan J. Lafaille, Lisa Bergman, Jocelyne Demengeot, Marta Caridade, Vanessa G. Oliveira, Luis Graca, Maria A. Curotto de Lafaille, and Ana Agua-Doce
- Subjects
0301 basic medicine ,Interleukin 2 ,Ovalbumin ,T cell ,Immunology ,Antigen presentation ,Population ,chemical and pharmacologic phenomena ,Aluminum Hydroxide ,Mice, Transgenic ,Biology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Antibodies ,Immune tolerance ,03 medical and health sciences ,Mice ,T-Lymphocyte Subsets ,medicine ,Immune Tolerance ,Immunology and Allergy ,Animals ,education ,Clonal Selection, Antigen-Mediated ,Cells, Cultured ,Mice, Knockout ,education.field_of_study ,Antigen Presentation ,FOXP3 ,Cell Differentiation ,Forkhead Transcription Factors ,Skin Transplantation ,Interleukin-10 ,Transplantation ,Tolerance induction ,030104 developmental biology ,medicine.anatomical_structure ,CD4 Antigens ,Interleukin-2 ,medicine.drug - Abstract
This deposit is composed by a publication in which the IGC' authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and could only be accessed by two ways: either by requesting a legal copy to the author (the email contact present in this deposit) or by visiting the following link: http://www.jimmunol.org/content/200/1/101.long#ack-1 This publication hasn't any creative commons license associated. It has been shown that dominant tolerance, namely in transplantation, requires Foxp3+regulatory T cells. Although most tolerance-inducing regimens rely on regulatory T cells, we found that induction of tolerance to proteins in aluminum hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4 Abs. This type of tolerance is Ag specific, and tolerant mice retain immune competence to respond to unrelated Ags. We demonstrated with chicken OVA-specific TCR-transgenic mice that the same tolerizing protocol (CD4 blockade) and the same target Ag (OVA) achieves Foxp3-dependent transplantation tolerance to OVA-expressing skin grafts, but Foxp3-independent tolerance when the Ag is provided as OVA-aluminum hydroxide. In the latter case, we found that tolerance induction triggered recessive mechanisms leading to elimination of effector cells and, simultaneously, a dominant mechanism associated with the emergence of an anergic and regulatory CTLA-4+IL-2lowFoxp3-T cell population, where the tolerance state is IL-10 dependent. Such Foxp3-independent mechanisms can improve the efficacy of tolerance-inducing protocols. Fundacao para a Ciencia e Tecnologia grant: (HMSP-ICT/0034/2013); FEDER through POR Lisboa 2020–Programa Operacional Regional de Lisboa grant: (LISBOA-01-0145-FEDER-007391). info:eu-repo/semantics/publishedVersion
- Published
- 2018
35. Adapting to the Coronavirus Pandemic: Building and Incorporating a Diagnostic Pipeline in a Shared Resource Laboratory.
- Author
-
Russell, Emma, Agua‐Doce, Ana, Carr, Lotte, Malla, Asha, Bartolovic, Kerol, Levi, Dina, Henderson, Carl, Das, Debipriya, Rhys, Hefin, Hobson, Philip, Purewal, Sukhveer, and Riddell, Andrew
- Abstract
In March 2020, with lockdown due to the coronavirus pandemic underway, the Francis Crick Institute (the Crick) regeared its research laboratories into clinical testing facilities. Two pipelines were established, one for polymerase chain reaction and the other for Serology. This article discusses the Cricks Flow Cytometry Science Technology Platform (Flow STP) role in setting up the Serology pipeline. Pipeline here referring to the overarching processes in place to facilitate the receipt of human sera through to a SARs‐CoV‐2 enzyme‐linked immunosorbent assay result. We examine the challenges that had to be overcome by a research laboratory to incorporate clinical diagnostics and the processes by which this was achieved. It describes the governance required to run the service, the design of the standard operating procedures (SOPs) and pipeline, the setting up of the assay, the validation required to show the robustness of the pipeline and reporting the results of the assay. Finally, as the lockdown started to ease in June 2020, it examines how this new service affects the daily running of the Flow STP. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
36. Human blood T fr cells are indicators of ongoing humoral activity not fully licensed with suppressive function
- Author
-
Ana Agua-Doce, Ana R. Pires, Susana L. Silva, Ana E. Sousa, Wim Pierson, F. N. Ribeiro, Válter R. Fonseca, Michelle A. Linterman, João Eurico Fonseca, Ana Raquel Maceiras, Luis Graca, Vasco C. Romão, and Repositório da Universidade de Lisboa
- Subjects
0301 basic medicine ,CD40 ,biology ,T cell ,Immunology ,Germinal center ,General Medicine ,Natural killer T cell ,3. Good health ,03 medical and health sciences ,Interleukin 21 ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,biology.protein ,medicine ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,030215 immunology - Abstract
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works, Germinal center (GC) responses are controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells and are crucial for the generation of high-affinity antibodies. Although the biology of human circulating and tissue Tfh cells has been established, the relationship between blood and tissue Tfr cells defined as CXCR5+Foxp3+T cells remains elusive. We found that blood Tfr cells are increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially in patients with high autoantibody titers, as well as in healthy individuals upon influenza vaccination. Although blood Tfr cells correlated with humoral responses, they lack full B cell–suppressive capacity, despite being able to suppress T cell proliferation. Blood Tfr cells have a naïve-like phenotype, although they are absent from human thymus or cord blood. We found that these cells were generated in peripheral lymphoid tissues before T-B interaction, as they are maintained in B cell–deficient patients. Therefore, blood CXCR5+Foxp3+ T cells in human pathology indicate ongoing humoral activity but are not fully competent circulating Tfr cells., This study was funded by HMSP-ICT/0034/2013, FAPESP/19906/2014, PTDC/IMI-IMU/7038/2014 research grants, and LISBOA-01-0145-FEDER-007391, projeto cofinanciado pelo FEDER através POR Lisboa 2020–Programa Operacional Regional de Lisboa, do PORTUGAL 2020, e pela Fundação para a Ciência e a Tecnologia. The vaccination study was funded by the European Research Council Starting Grant TWILIGHT (to M.A.L.). W.P. was funded by a Newton International Fellowship from the Royal Society. M.A.L. was funded by the Bioscience and Biotechnology Research Council.
- Published
- 2017
37. Human blood T
- Author
-
Valter R, Fonseca, Ana, Agua-Doce, Ana Raquel, Maceiras, Wim, Pierson, Filipa, Ribeiro, Vasco C, Romão, Ana Rita, Pires, Susana Lopes, da Silva, João Eurico, Fonseca, Ana E, Sousa, Michelle A, Linterman, and Luis, Graca
- Subjects
Article - Abstract
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells and are crucial for the generation of high affinity antibodies. Although the biology of human circulating and tissue Tfh cells has been established, the relationship between blood and tissue Tfr cells, defined as CXCR5(+)Foxp3(+) T cells, remains elusive. Here, we found that blood Tfr cells are increased in Sjögren syndrome, especially in patients with high autoantibody titres, as well as in healthy subjects upon influenza vaccination. While, blood Tfr cells correlated with humoral responses they lack full B-cell suppressive capacity, despite being able to suppress T-cell proliferation. Blood Tfr cells have a naïve-like phenotype, although they are absent from human thymus or cord blood. Here, we found these cells were generated in peripheral lymphoid tissues prior to T-B interaction, as they are maintained in B-cell deficient patients. Therefore, blood CXCR5(+)Foxp3(+) T cells in human pathology indicate ongoing humoral activity, but are not competent Tfr cells.
- Published
- 2017
38. Reply
- Author
-
Ana Agua-Doce, João Eurico Fonseca, Válter R. Fonseca, Luis Graca, and Vasco C. Romão
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,T cell ,Immunology ,T-Lymphocytes, Helper-Inducer ,Stratification (mathematics) ,03 medical and health sciences ,Sjogren's Syndrome ,030104 developmental biology ,medicine.anatomical_structure ,Rheumatology ,Internal medicine ,Follicular phase ,Humans ,Immunology and Allergy ,Medicine ,Sjogren s ,business ,Biomarkers - Published
- 2018
39. T Follicular Regulatory Cells Are Decreased in Patients With Established Treated Rheumatoid Arthritis With Active Disease: Comment on the Article by Liu et al
- Author
-
Romão, Vasco C., primary, Fonseca, João Eurico, additional, Agua-Doce, Ana, additional, and Graca, Luis, additional
- Published
- 2018
- Full Text
- View/download PDF
40. Reply
- Author
-
Fonseca, Valter R., primary, Romão, Vasco C., additional, Fonseca, João Eurico, additional, Agua-Doce, Ana, additional, and Graca, Luis, additional
- Published
- 2018
- Full Text
- View/download PDF
41. THU0045 Expansion of activated cxcr5+icos+ tfh cells and plasmablasts induced by seasonal influenza vaccine is impaired in anti-il-6r treated rheumatoid arthritis patients
- Author
-
Romao, V.C., primary, Agua-Doce, A., additional, Polido-Pereira, J., additional, Barros, R., additional, Lopes, I.P., additional, Seixas, M.I., additional, Saavedra, M.J., additional, Sacadura-Leite, E., additional, Rebelo-de-Andrade, H., additional, Fonseca, J.E., additional, and Graca, L., additional
- Published
- 2018
- Full Text
- View/download PDF
42. The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome
- Author
-
Fonseca, Valter R., primary, Romão, Vasco C., additional, Agua-Doce, Ana, additional, Santos, Mara, additional, López-Presa, Dolores, additional, Ferreira, Ana Cristina, additional, Fonseca, João Eurico, additional, and Graca, Luis, additional
- Published
- 2018
- Full Text
- View/download PDF
43. Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance
- Author
-
Agua-Doce, Ana, primary, Caridade, Marta, additional, Oliveira, Vanessa G., additional, Bergman, Lisa, additional, Lafaille, Maria C., additional, Lafaille, Juan J., additional, Demengeot, Jocelyne, additional, and Graca, Luis, additional
- Published
- 2018
- Full Text
- View/download PDF
44. Umbilical cord tissue-derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing
- Author
-
Pedro E. Cruz, Mariana Filipe, Maria Manuela Gaspar, Ana Agua-Doce, Augusto Ministro, Joana P. Miranda, Sandra Simões, Luis Graca, Mariana Teixeira, Jorge M. Santos, Ana Santos Pereira, Manuela Carvalheiro, Rita N. Bárcia, Helder Cruz, and Susana Constantino Rosa Santos
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Stromal cell ,Angiogenesis ,Immunology ,Population ,Neovascularization, Physiologic ,Biology ,Mesenchymal Stem Cell Transplantation ,Cryopreservation ,Immunophenotyping ,Umbilical Cord ,Immunomodulation ,03 medical and health sciences ,Mice ,In vivo ,Freezing ,Immunology and Allergy ,Animals ,Humans ,Rats, Wistar ,education ,Genetics (clinical) ,Cells, Cultured ,Transplantation ,education.field_of_study ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Flow Cytometry ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,Oncology ,Cancer research ,CD146 ,Human umbilical vein endothelial cell ,Female - Abstract
Background aims The effect of cryopreservation on mesenchymal stromal cell (MSC) therapeutic properties has become highly controversial. However, data thus far have indiscriminately involved the assessment of different types of MSCs with distinct production processes. This study assumed that MSC-based products are affected differently depending on the tissue source and manufacturing process and analyzed the effect of cryopreservation on a specific population of umbilical cord tissue–derived MSCs (UC-MSCs), UCX ® . Methods Cell phenotype was assessed by flow cytometry through the evaluation of the expression of relevant surface markers such as CD14, CD19, CD31, CD34, CD44, CD45, CD90, CD105, CD146, CD200, CD273, CD274 and HLA-DR. Immunomodulatory activity was analyzed in vitro through the ability to inhibit activated T cells and in vivo by the ability to reverse the signs of inflammation in an adjuvant-induced arthritis (AIA) model. Angiogenic potential was evaluated in vitro using a human umbilical vein endothelial cell–based angiogenesis assay, and in vivo using a mouse model for hindlimb ischemia. Results Phenotype and immunomodulatory and angiogenic potencies of this specific UC-MSC population were not impaired by cryopreservation and subsequent thawing, both in vitro and in vivo . Discussion This study suggests that potency impairment related to cryopreservation in a given tissue source can be avoided by the production process. The results have positive implications for the development of advanced-therapy medicinal products.
- Published
- 2016
45. Regulatory T Cells
- Author
-
Luis Graca, Rita I. Azevedo, Marta Monteiro, Ana Agua-Doce, and João F. Lacerda
- Subjects
education.field_of_study ,Lymphocyte ,T cell ,Population ,Peripheral tolerance ,FOXP3 ,hemic and immune systems ,chemical and pharmacologic phenomena ,Biology ,medicine.disease_cause ,Autoimmunity ,Interleukin 10 ,medicine.anatomical_structure ,CTLA-4 ,Immunology ,medicine ,education - Abstract
Foxp3 + CD4 T cells are a specialized regulatory T (Treg) lymphocyte population that plays a unique role in maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammation. However, deregulated action of Treg cells may also limit beneficial responses by suppressing immunity against microbes and tumors. Tregs are generated during the normal process of T cell development in the thymus, but may also differentiate in the periphery from conventional T cells. In addition to development, Treg cells are also heterogeneous regarding functional activity, migratory potential, and activation status. Because they have a great impact on the balance between tolerance and autoimmunity, there is great interest in understanding Treg generation, diversity, activation requirements, stability, trafficking, homeostasis, and mechanisms of action in vivo for the development of therapeutic strategies to modulate Treg function in the clinic. In this chapter, we will discuss these topics in the light of current knowledge of the Treg field.
- Published
- 2016
46. Contributors
- Author
-
A. Agua-Doce, O. Awe, R.I. Azevedo, R. Bacchetta, R. Bortell, M.A. Brehm, A.N. Burska, K. Csomos, J.C. Denny, J.T. Dudley, J. Farmer, D.R. Getts, L. Graca, D.L. Greiner, S.R. Harrison, S. Hillion, M.H. Kaplan, B.A. Kidd, J.F. Lacerda, Y.N. Lee, S.D. Miller, M. Monteiro, F. Ponchel, L.D. Shultz, Q. Simon, C.B. Smarr, H. Ueno, M. Verma, J.E. Walter, J.L. Warner, and Jianfei Yang
- Published
- 2016
47. Monoclonal anti-CD8 therapy induces disease amelioration in the K/BxN mouse model of spontaneous chronic polyarthritis
- Author
-
Paulo Rodrigues-Santos, Helena Carvalheiro, Lina Carvalho, Bruno Raposo, Ana Agua-Doce, José António Pereira da Silva, Luis Graca, M. Margarida Souto-Carneiro, and Repositório da Universidade de Lisboa
- Subjects
Immunoconjugates ,Artrite Experimental ,CD8 Antigens ,T-Lymphocytes ,medicine.medical_treatment ,T cell ,Immunology ,Antigénio CD8 ,Arthritis ,Mice, Transgenic ,CD8-Positive T-Lymphocytes ,Antigens, CD8 ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Anticorpos Monoclonais ,Rheumatology ,Mice, Inbred NOD ,medicine ,Animals ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Antibodies, monoclonal ,030304 developmental biology ,0303 health sciences ,Synovitis ,biology ,business.industry ,medicine.disease ,Arthritis, Experimental ,3. Good health ,Mice, Inbred C57BL ,Granzyme B ,Cytokine ,medicine.anatomical_structure ,Granzyme ,biology.protein ,Tumor necrosis factor alpha ,business ,CD8 ,030215 immunology - Abstract
© 2010, American College of Rheumatology, Objective. CD8+ T cells are part of the T cell pool infiltrating the synovium in rheumatoid arthritis (RA). However, their role in the pathogenesis of RA has not been fully delineated. Using the K/BxN mouse model of spontaneous chronic arthritis, which shares many similarities with RA, we studied the potential of CD8 T cell depletion with monoclonal antibodies (mAb) to stop and reverse the progression of experimental arthritis. Methods. CD8+ T cells from the blood and articular infiltrate of K/BxN mice were characterized for cell surface phenotypic markers and for cytokine production. Additionally, mice were treated with specific anti-CD8 mAb (YTS105 and YTS169.4), with and without thymectomy. Results. CD8+ T cells from the peripheral blood and joints of K/BxN mice were mainly CD69+ and CD62L-CD27+ T cells expressing proinflammatory cytokines (interferon-γ [IFNγ], tumor necrosis factor α [TNFα], interleukin-17a [IL-17A], and IL-4), and granzyme B. In mice receiving anti-CD8 mAb, the arthritis score improved 5 days after treatment. Recovery of the CD8+ T cells was associated with a new increase in the arthritis score after 20 days. In thymectomized and anti-CD8 Ab–treated mice, the arthritis score improved permanently. Histologic analysis showed an absence of inflammatory infiltrate in the anti-CD8 mAb–treated mice. In anti-CD8 mAb–treated mice, the serologic levels of TNFα, IFNγ, IL-6, and IL-5 normalized. The levels of the disease-related anti–glucose-6-phosphate isomerase antibodies did not change. Conclusion. These results indicate that synovial activated effector CD8 T cells locally synthesize proinflammatory cytokines (IFNγ, TNFα, IL-17, IL-6) and granzyme B in the arthritic joint, thus playing a pivotal role in maintaining chronic synovitis in the K/BxN mouse model of arthritis., Mr. Raposo’s work was supported by the Instituto do Emprego e Formação Profissional (grant 266/EP/2006) and the Fundação para a Ciência e Tecnologia (grant SFRH/BD/40658/2007). Ms Carvalheiro’s work was supported by the Fundação para a Ciência e Tecnologia (grant SFRH/BD/60467/2009). Dr. Graça’s work was supported by the Fundação para a Ciência e Tecnologia (grant POCI/SAU-MMO/55974/2004). Dr. Souto-Carneiro’s work was supported by a Marie Curie Intra-European Fellowship (LIF-025885) and a EULAR Young Investigator Award.
- Published
- 2010
48. Identification of Regulatory Foxp3+ Invariant NKT Cells Induced by TGF-β
- Author
-
Catarina F. Almeida, Marta Monteiro, Marta Caridade, Ivonne Wollenberg, Luis Graca, Joana Duarte, Ana Agua-Doce, Bruno Silva-Santos, Julie C. Ribot, and Repositório da Universidade de Lisboa
- Subjects
Male ,Adoptive cell transfer ,Cellular differentiation ,Immunology ,Population ,Galactosylceramides ,chemical and pharmacologic phenomena ,Biology ,T-Lymphocytes, Regulatory ,Mice ,Invariant NKT (iNKT) cells ,Cell Movement ,Transforming Growth Factor beta ,medicine ,Animals ,Immunology and Allergy ,Foxp3+ ,education ,Cells, Cultured ,Mice, Knockout ,Mice, Inbred BALB C ,education.field_of_study ,Encephalomyelitis, autoimmune, experimental ,Experimental autoimmune encephalomyelitis ,T-cell receptor ,FOXP3 ,Cell Differentiation ,Forkhead Transcription Factors ,hemic and immune systems ,Transforming growth factor beta ,Flow Cytometry ,medicine.disease ,Natural killer T cell ,Cell biology ,Mice, Inbred C57BL ,Liver ,Natural killer T-cells ,biology.protein ,Female ,Lymph Nodes - Abstract
©2010 by The American Association of Immunologists, Inc. All rights reserved., Invariant NKT (iNKT) cells were shown to prevent the onset of experimental autoimmune encephalomyelitis in mice following administration of their specific TCR agonist alpha-galactosylceramide. We found that this protection was associated with the emergence of a Foxp3(+) iNKT cell population in cervical lymph nodes. We demonstrate that the differentiation of these cells is critically dependent on TGF-beta in both mice and humans. Moreover, in vivo generation of Foxp3(+) iNKT cells was observed in the TGF-beta-rich environment of the murine gut. Foxp3(+) iNKT cells displayed a phenotype similar to that of Foxp3(+) regulatory T cells, and they suppress through a contact-dependent, glucocorticoid-induced TNFR-mediated mechanism. Nevertheless, Foxp3(+) iNKT cells retain distinctive NKT cell characteristics, such as promyelocytic leukemia zinc finger protein expression and preferential homing to the liver following adoptive transfer, where they stably maintained Foxp3 expression. Our data thus unveil an unexpected capacity of iNKT cells to acquire regulatory functions that may contribute to the establishment of immunological tolerance., This work was supported by Grants PIC/IC/82895/2007 and PTDC/SAU-MII/64279/2006 from the Fundação para a Ciência e Tecnologia, Grant Immunonet-SOE1/1P1/E014 from Sudoe (to L.G.), and Grant YIP 1440 from the European Molecular Biology Organization (to B.S.S.).
- Published
- 2010
49. Human blood T fr cells are indicators of ongoing humoral activity not fully licensed with suppressive function
- Author
-
Fonseca, Valter R., primary, Agua-Doce, Ana, additional, Maceiras, Ana Raquel, additional, Pierson, Wim, additional, Ribeiro, Filipa, additional, Romão, Vasco C., additional, Pires, Ana Rita, additional, da Silva, Susana Lopes, additional, Fonseca, João Eurico, additional, Sousa, Ana E., additional, Linterman, Michelle A., additional, and Graca, Luis, additional
- Published
- 2017
- Full Text
- View/download PDF
50. Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells
- Author
-
Ivan Maillard, Manuel Rebelo, Ana Agua Doce, Margarida Albuquerque Almeida Santos, Jocelyne Demengeot, Alexis Dumortier, Leonor Parreira, Leonor Morais Sarmento, Warren S. Pear, Freddy Radtke, and Hélia Neves
- Subjects
Lipopolysaccharides ,Cellular differentiation ,T cell ,B-cell receptor ,Notch signaling pathway ,Immunoglobulins ,Biology ,Ligands ,Mice ,Serrate-Jagged Proteins ,medicine ,Animals ,Receptor, Notch1 ,B cell ,B-Lymphocytes ,Multidisciplinary ,Dose-Response Relationship, Drug ,Receptors, Notch ,Calcium-Binding Proteins ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Cell Differentiation ,Biological Sciences ,Molecular biology ,Cell biology ,Mice, Inbred C57BL ,B-1 cell ,medicine.anatomical_structure ,Intercellular Signaling Peptides and Proteins ,Jagged-1 Protein ,Spleen - Abstract
Notch signaling regulates B and T lymphocyte development and T cell effector class decision. In this work, we tested whether Notch activity affects mature B cell activation and differentiation to antibody-secreting cells (ASC). We show increased frequency of ASC in cultures of splenic B cells activated with LPS or anti-CD40 when provided exogenous Notch ligand Delta-like-1 (Dll1). Our results indicate that Notch–Dll1 interaction releases a default pathway that otherwise inhibits Ig secretion upon B cell activation. Thus, Dll1 enhanced spontaneous Ig secretion by naturally activated marginal zone B and B1 cells and reversed the inhibition of ASC differentiation mediated by B cell receptor crosslinking during LPS. Moreover, suppression of Notch signaling in B cell expression of either a dominant-negative mutant form of Mastermind-like 1 or a null mutation of Notch1 not only prevented Dll1-mediated enhancement of ASC differentiation but also reduced dramatically LPS-induced Ig secretion. Finally, we show that Dll1 and Jagged-1 are differentially expressed in discrete areas of the spleen, and that the effect of Notch engagement on Ig secretion is ligand-specific. These results indicate that Notch ligands participate in the definition of the mature B cell microenvironment that influences their terminal differentiation.
- Published
- 2007
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.