22 results on '"Isabelle Peguillet"'
Search Results
2. Data from Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer
- Author
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Yohann Loriot, Laurence Zitvogel, Jean-Yves Scoazec, Guido Kroemer, Miriam Merad, Fabrice Andre, Benjamin Besse, Michiel S. Van Der Heijden, Nick Van Dijk, Jeroen Van Dorp, Aurélien Marabelle, Lisa Derosa, Gwénaël Le Teuff, Florent Ginhoux, Mathieu Rouanne, Jacques Fieschi, Yves Allory, Camelia Radulescu, Etienne Rouleau, Romain Daillere, Adeline Mallet, Maryse Moya-Nilges, Nadège Cayet, Ivo Gomperts Boneca, Shaima Belhechmi, Baptiste Archambaud, Thibault Raoult, Aymeric Silvin, Kevin Mulder, Garett Dunsmore, François-Xavier Danlos, Camille Bleriot, Jacques Bou Khalil, Gabriel Haddad, Caroline Davin, Mounia Filahi, Thomas Sbarrato, Allan Sauvat, Nicolas Signolle, Virginie Marty, Pierre Ly, Caroline Flament, Marine Mazzenga, Agathe Dubuisson, Idir Ouzaid, Evanguelos Xylinas, Morgan Roupret, Luca Campedel, Carole Helissey, Gwenaelle Gravis, Géraldine Pignot, François Audenet, Constance Thibault, Cédric Lebacle, Cassandra Thelemaque, Maxime Descartes Mbogning-Fonkou, Marianne Gazzano, Isabelle Peguillet, Carolina Alves Costa Silva, Leonardo Lordello, and Anne-Gaëlle Goubet
- Abstract
Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale.Significance:In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli–specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies.This article is highlighted in the In This Issue feature, p. 2221
- Published
- 2023
3. Escherichia coli-Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer
- Author
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Anne-Gaëlle Goubet, Leonardo Lordello, Carolina Alves Costa Silva, Isabelle Peguillet, Marianne Gazzano, Maxime Descartes Mbogning-Fonkou, Cassandra Thelemaque, Cédric Lebacle, Constance Thibault, François Audenet, Géraldine Pignot, Gwenaelle Gravis, Carole Helissey, Luca Campedel, Morgan Roupret, Evanguelos Xylinas, Idir Ouzaid, Agathe Dubuisson, Marine Mazzenga, Caroline Flament, Pierre Ly, Virginie Marty, Nicolas Signolle, Allan Sauvat, Thomas Sbarrato, Mounia Filahi, Caroline Davin, Gabriel Haddad, Jacques Bou Khalil, Camille Bleriot, François-Xavier Danlos, Garett Dunsmore, Kevin Mulder, Aymeric Silvin, Thibault Raoult, Baptiste Archambaud, Shaima Belhechmi, Ivo Gomperts Boneca, Nadège Cayet, Maryse Moya-Nilges, Adeline Mallet, Romain Daillere, Etienne Rouleau, Camelia Radulescu, Yves Allory, Jacques Fieschi, Mathieu Rouanne, Florent Ginhoux, Gwénaël Le Teuff, Lisa Derosa, Aurélien Marabelle, Jeroen Van Dorp, Nick Van Dijk, Michiel S. Van Der Heijden, Benjamin Besse, Fabrice Andre, Miriam Merad, Guido Kroemer, Jean-Yves Scoazec, Laurence Zitvogel, Yohann Loriot, Université Paris-Saclay, Institut Gustave Roussy (IGR), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), Institut Curie [Paris], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Direction de la recherche clinique [Gustave Roussy], Service de biostatistique et d'épidémiologie (SBE), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Département de médecine oncologique [Gustave Roussy], Département de biologie et pathologie médicales [Gustave Roussy], Oncologie gynécologique, ANR-16-RHUS-0008, ANR-21-RHUS-0017, Bristol-Myers Squibb, BMS, Pfizer, Astellas Pharma US, APUS, AstraZeneca, Genentech, Merck, Roche, Gilead Sciences, Meso Scale Diagnostics, MSD, Janssen Pharmaceuticals, Merck Sharp and Dohme, MSD, Horizon 2020 Framework Programme, H2020: 19-CE15-0029-01, 825410, Clovis Oncology, Seerave Foundation, Fondation Philanthropia, Advanced Accelerator Applications, AAA, Agence Nationale de la Recherche, ANR: ANR-10-LABX-62-IBEID, Fondation pour la Recherche Médicale, FRM, Daiichi-Sankyo, Fondation ARC pour la Recherche sur le Cancer, ARC, Ligue Contre le Cancer, Institut Universitaire de France, IUF, Institut National Du Cancer, INCa, Cancéropôle Ile de France, Association Française d'Urologie, AFU, Labex Immuno-Oncology, The trial was conducted by the French Genitourinary Group (GETUG) and funded by MSD, which provided the drug. This study was approved by the ethics committee CPP Est-III in December 2017 and the French National Agency for the Safety of Medicines and Health Products (ANSM) in November 2017, and was conducted in accordance with the protocols and Good Clinical Practice Guidelines defined by the International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and the principles of the Declaration of Helsinki., C. Alves Costa Silva reports grants from MSD Avenir Foundation during the conduct of the study. C. Thibault reports personal fees and nonfinancial support from Pfizer, Merck, MSD, Janssen, and Ipsen, grants, personal fees, and nonfinancial support from AstraZeneca, We thank pathologists, nurses, and clinical research associates from Hôpital Européenn George Pompidou, Hôpital Begin, Institut Paoli-Calmettes, Hôpital Bichat, and Hôpital Pitié-Salpétrière for their participation in the PANDORE clinical trial. We are thankful to the flow and mass cytometry facility team of Gustave Roussy (Philippe Rameau and Cyril Catelain). We thank Fluidigm for their support. We are grateful for support for equipment from the French Government Programme Investissements d’Avenir France BioImag-ing (FBI, No. ANR-10-INSB-04-01) and the French Government (Agence Nationale de la Recherche) Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). A.-G. Goubet was supported by Fondation pour la Recherche Médicale. C. Alves Costa Silva was supported by MSD Avenir. F.-X. Danlos was supported by Fondation Philantropia. M. Roupret was supported by Fondation Foch and the Association Française d’Urologie (AFU). L. Zitvogel was funded by the RHU Torino Lumière (ANR-16-RHUS-0008). L. Zitvogel and L. Derosa were supported by RHU5 'ANR-21-RHUS-0017' IMMUNOLIFE, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), as well as the SIGN’IT ARC foundation. L. Zitvogel was supported by European Union’s Horizon 2020 research and innovation programme under grant agreement number 825410 [project acronym: ONCOBIOME, project title: Gut OncoMicrobiome Signatures (GOMS) associated with cancer incidence, prognosis, and prediction of treatment response]. L. Zitvogel also received an ANR grant–French-German Ileobiome 19-CE15-0029-01. L. Zitvogel and G. Kroemer received a donation from the Seerave Foundation. L. Zitvogel and G. Kroemer were supported by the Ligue contre le Cancer (équipe labelisée), ANR projets blancs, Cancéropôle Ile-de-France, Fondation pour la Recherche Médicale (FRM), a donation by Elior, Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, the LabEx Immuno-Oncology, and FHU CARE, Dassault, and Badinter Philantropia. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact., Bristol Myers Squibb, and Sanofi, and personal fees from Astellas and AAA during the conduct of the study, as well as personal fees and nonfinancial support from Pfizer, Merck, MSD, Janssen, and Ipsen, grants, personal fees, and nonfinancial support from AstraZeneca, Bristol Myers Squibb, and Sanofi, and personal fees from Astellas and AAA outside the submitted work. F. Audenet reports personal fees from Astellas, Urodiag, Vitadx, and Bristol Myers Squibb, and nonfinancial support from Ipsen outside the submitted work. G. Gravis reports grants from Bristol Myers Squibb, and other support from MSD, Bristol Myers Squibb, and Merck–Pfizer alliance outside the submitted work. C. Helissey reports personal fees from Janssen-Cilag, Roche, Bayer, AstraZeneca, and Astellas outside the submitted work. L. Cam-pedel reports personal fees from MSD, Pfizer, Bristol Myers Squibb, and Bayer outside the submitted work. T. Sbarrato reports personal fees from Veracyte during the conduct of the study. T. Raoult reports grants, personal fees, and nonfinancial support from Merck Sharp & Dohme during the conduct of the study. E. Rouleau reports grants from AstraZeneca, Roche, Clovis, Bristol Myers Squibb, and MSD outside the submitted work. Y. Allory reports other support from Astra-Zeneca, MSD, and Bristol Myers Squibb outside the submitted work. J. Fieschi reports personal fees from Veracyte during the conduct of the study. A. Marabelle reports grants, personal fees, nonfinancial support, and other support from MSD, Bristol Myers Squibb, and AstraZeneca, and personal fees, nonfinancial support, and other support from Roche/Genentech and Pfizer outside the submitted work. J. Van Dorp reports other support from Bristol Myers Squibb during the conduct of the study. M.S. van der Heijden reports grants from Bristol Myers Squibb during the conduct of the study, as well as grants and personal fees from Bristol Myers Squibb, Roche, and AstraZeneca, grants from 4SC, and personal fees from MSD/Merck, Janssen, Pfizer, and Seagen outside the submitted work. B. Besse reports grants from 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Chu-gai Pharmaceutical, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, Eisai, Genzyme Corporation, GSK, Inivata, Ipsen, Janssen, Onxeo, OSE Immunotherapeutics, Pfizer, Roche/Genentech, Sanofi, Takeda, Tolero Pharmaceuticals, and Turning Point Therapeutics during the conduct of the study. F. Andre reports grants and other support from AstraZeneca and Daiichi Sankyo, grants from Lilly and Sanofi, and other support from Novartis and Relay outside the submitted work. M. Merad reports grants and personal fees from Regeneron, personal fees from Compugen, Morphic Therapeutics, Myeloid Therapeutics, Nirogy, DrenBio, Oncoresponse, Asherbio, Pionyr, Owkin, and Larkspur, other support from Innate Pharma, Genenta, DBV, and OSE Immunotherapeutics, and grants from Boehringer outside the submitted work. G. Kroemer reports grants from Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Sotio, Tollys, Vascage, and Vasculox/Tioma, and personal fees from Reithera outside the submitted work, is on the Board of Directors for Bristol Myers Squibb Foundation France, and is a scientific cofounder of EverImmune, Osasuna Therapeutics, Samsara Therapeutics, and Therafast Bio. L. Zitvogel reports grants and personal fees from EverImmune, and grants from 9 Meters and Pileje during the conduct of the study, grants from Daiichi Sankyo outside the submitted work, and a patent for B220028EPA pending. Y. Loriot reports grants from MSD and personal fees from MSD during the conduct of the study, personal fees from Bristol Myers Squibb, Pfizer, Merck Serono, AstraZeneca, Seattle Genetics, Gilead, Taiho, and Astel-las, grants and personal fees from Janssen, and grants from Roche and Celsius outside the submitted work, and a patent for EP2305181.4 pending. No disclosures were reported by the other authors., and FHU CARE, Dassault, and Badinter Philantropia., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), and ANR-21-RHUS-0017,IMMUNOLIFE,Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors(2021)
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[SDV]Life Sciences [q-bio] ,Muscles ,Programmed Cell Death 1 Receptor ,T-Lymphocytes, Helper-Inducer ,Chemokine CXCL13 ,B7-H1 Antigen ,Neoadjuvant Therapy ,Treatment Outcome ,Oncology ,Urinary Bladder Neoplasms ,Immunoglobulin G ,Escherichia coli ,Humans ,Immune Checkpoint Inhibitors - Abstract
Biomarkers guiding the neoadjuvant use of immune-checkpoint blockers (ICB) are needed for patients with localized muscle-invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline and the induction of tertiary lymphoid structures after pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium-invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale. Significance: In patients with bladder cancer treated with neoadjuvant pembrolizumab, E. coli–specific CXCL13 producing TFH and IgG constitute biomarkers that predict clinical benefit. Beyond its role as a biomarker, such immune responses against E. coli might be harnessed for future therapeutic strategies. This article is highlighted in the In This Issue feature, p. 2221
- Published
- 2022
4. Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge
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John E. Bradley, Jessica N. Peel, Guang Yang, Todd Green, M. Scot Roberts, Kevin S. Harrod, Amelia K. Pinto, Christopher A. Risley, Aaron Silva-Sanchez, James D. Brien, Alexandria M Dickson, Fen Zhou, Young Ho Lee, Selene Meza-Perez, Davide Botta, John J Suschak, Tsungwei Feng, Vyjayanthi Krishnan, Brittany Dean, Jianfeng Zhang, Esther Zumaquero, Shihong Qiu, Thomas S. Simpler, Bethlehem Shiberu, Isabelle Peguillet, Bertrand Georges, Qiao Shang, R Glenn King, Jennifer L. Tipper, John T. Killian, S. Rameeza Allie, Troy D. Randall, Betty Mousseau, Mingyong Liu, Frances E. Lund, and Michael D. Schultz
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Immunology ,Viral vector ,Immune system ,Immunity ,vaccine ,Drug Discovery ,medicine ,Pharmacology (medical) ,Pharmacology ,receptor binding domain ,biology ,business.industry ,SARS-CoV-2 ,intranasal ,viral vector ,adenovirus vector ,COVID-19 ,Vaccination ,Infectious Diseases ,medicine.anatomical_structure ,biology.protein ,mucosal immunity ,Medicine ,Nasal administration ,Antibody ,business ,IgA ,CD8 ,Respiratory tract - Abstract
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.
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- 2021
5. Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice
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John T. Killian, Rameeza Allie, Guang Yang, Brittany Dean, Jianfeng Zhang, Young H Lee, John E. Bradley, Esther Zumaquero, Christopher A. Risley, Shihong Qiu, Jennifer L. Tipper, Troy D. Randall, Selene Meza-Perez, Kevin S. Harrod, Aaron Silva-Sanchez, Qiao Shang, Vyjayanthi Krishnan, Betty Mousseau, Isabelle Peguillet, Rodney G. King, Fen Zhou, Mingyong Liu, Jessica N. Peel, Bertrand Georges, Frances E. Lund, Todd Green, Michael D. Schultz, Bethlehem Shiberu, Thomas S. Simpler, Ray Feng, Scot Roberts, and Davide Botta
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viruses ,Mucous membrane of nose ,medicine.disease_cause ,Article ,Immune system ,vaccine ,medicine ,Coronavirus ,Lung ,receptor binding domain ,biology ,business.industry ,SARS-CoV-2 ,intranasal ,viral vector ,adenovirus vector ,COVID-19 ,biochemical phenomena, metabolism, and nutrition ,Vaccination ,medicine.anatomical_structure ,Immunology ,biology.protein ,mucosal immunity ,Nasal administration ,Antibody ,business ,CD8 ,IgA - Abstract
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.
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- 2020
6. Publisher Correction: Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
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Vincent Rouilly, Cherie Green, Lluis Quintana-Murci, Julie Hunkapiller, Isabelle Peguillet, Magnus Fontes, Jacob Bergstedt, Alejandra Urrutia, Claire Leloup, Benoit Beitz, Friederike Jönsson, Darragh Duffy, Stéphanie Thomas, François Huetz, Lars Rogge, Cécile Alanio, Matthew L. Albert, Petar Scepanovic, Olivier Lantz, Barbara Piasecka, Yoong Wearn Lim, Jacques Fellay, Hélène Quach, Christian Hammer, Milena Hasan, Etienne Patin, Magge Zepeda, Valentina Libri, and James P. Di Santo
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0301 basic medicine ,Innate immune system ,Immunology ,Computational biology ,Biology ,Natural variation ,InformationSystems_GENERAL ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Correct name ,Immunology and Allergy - Abstract
In the version of this article initially published, the name of one author was incorrect (James P. Santo). The correct name is James P. Di Santo. The error has been corrected in the HTML and PDF versions of the article.
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- 2018
7. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
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Petar Scepanovic, Julie Hunkapiller, Jacob Bergstedt, Alejandra Urrutia, Jacques Fellay, Lluis Quintana-Murci, Hélène Quach, Friederike Jönsson, Cherie Green, Olivier Lantz, Lars Rogge, Stéphanie Thomas, Vincent Rouilly, Barbara Piasecka, Yoong Wearn Lim, Claire Leloup, Cécile Alanio, Isabelle Peguillet, Christian Hammer, Benoit Beitz, Magnus Fontes, Magge Zepeda, Matthew L. Albert, Valentina Libri, James P. Di Santo, Etienne Patin, Milena Hasan, François Huetz, Darragh Duffy, Vougny, Marie-Christine, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Lund University [Lund], Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Anticorps en Thérapie et Pathologie, Genentech, Inc. [San Francisco], Immunorégulation, Biologie des Populations Lymphocytaires, Institut Curie [Paris], International Group for Data Analysis (IGDA), Immunité Innée - Innate Immunity, This work benefited from support of the French government’s program ‘Investissement d’Avenir’, managed by the Agence Nationale de la Recherche (reference 10-LABX-69-01). J.B. is a member of the LCCC Linnaeus Center and the ELLIIT Excellence Center at Lund University and is supported by the ELLIIT Excellence Center., The Milieu Intérieur Consortium : Laurent Abel, Andres Alcover, Kalle Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James P. Di Santo, Françoise Dromer, Darragh Duffy, Gérard Eberl, Jost Enninga, Jacques Fellay, Antonio Freitas, Odile Gelpi, Ivo Gomperts Boneca, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Marie-Noëlle Ungeheuer, Lluís Quintana-Murci & Matthew L. Albert, ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne (UNIL), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
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Adult ,Male ,0301 basic medicine ,MESH: Immunity, Innate/genetics ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,MESH: Immunophenotyping ,MESH: Genetic Variation/immunology ,Immunology ,Genome-wide association study ,Disease ,Adaptive Immunity ,Biology ,Immunophenotyping ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Genetic variation ,Humans ,Immunology and Allergy ,Aged ,Genetic association ,MESH: Aged ,Innate immune system ,MESH: Humans ,MESH: Middle Aged ,Genetic Variation ,MESH: Adult ,Environmental exposure ,Middle Aged ,Immunity, Innate ,MESH: Male ,3. Good health ,030104 developmental biology ,MESH: Young Adult ,MESH: Genome-Wide Association Study ,MESH: Adaptive Immunity/genetics ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,MESH: Female ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
A Publisher Correction to this article was published on 03 May 2018; International audience; The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.
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- 2018
8. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC
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Alain Livartoski, Melinda Charrier, Ludovic Lacroix, Inka Zoernig, Eric Dansin, Olivier Lantz, Benjamin Besse, Nadege Vimond, Kavita M. Dhodapkar, Jean-Charles Soria, Isabelle Peguillet, Frédéric Vély, Madhav V. Dhodapkar, Elke Pogge von Strandmann, Katrin S. Reiners, Clotilde Théry, Nathalie Chaput, Alexander M.M. Eggermont, Sophie Viaud, Agnès Laplanche, Thierry Le Chevalier, David Planchard, Fabrice Barlesi, Laurence Zitvogel, Valérie Lapierre, Sylvie Rusakiewicz, Stéphanie Ploix, Jonathan M. Pitt, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
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0301 basic medicine ,medicine.medical_treatment ,T cell ,Immunology ,exosomes ,NSCLC ,03 medical and health sciences ,MHC class I ,polycyclic compounds ,Immunology and Allergy ,Medicine ,NK cell ,phase II trial ,Original Research ,MHC class II ,biology ,business.industry ,Induction chemotherapy ,Dendritic cell ,Immunotherapy ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Tumor progression ,biology.protein ,Cancer research ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cancer vaccine ,immunotherapy ,business ,cancer vaccine ,hormones, hormone substitutes, and hormone antagonists - Abstract
International audience; Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN―free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN―Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN―Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN―Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN―Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC.
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- 2015
9. High numbers of differentiated effector CD4 T cells are found in patients with cancer and correlate with clinical response after neoadjuvant therapy of breast cancer
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Thierry Dorval, Sophie Piperno-Neumann, Maud Milder, Suzy Scholl, Isabelle Peguillet, Anne Vincent-Salomon, Delphine Louis, and Olivier Lantz
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CD4-Positive T-Lymphocytes ,Uveal Neoplasms ,Cancer Research ,Population ,Breast Neoplasms ,Docetaxel ,Cancer Vaccines ,Breast cancer ,T-Lymphocyte Subsets ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Cytotoxic T cell ,Humans ,IL-2 receptor ,Leukapheresis ,education ,Interleukin-7 receptor ,Cyclophosphamide ,Melanoma ,Epirubicin ,education.field_of_study ,business.industry ,Cancer ,Interleukin ,Cell Differentiation ,medicine.disease ,Neoadjuvant Therapy ,Oncology ,Immunology ,Female ,Taxoids ,Fluorouracil ,business ,CD8 - Abstract
CD4+ T cells influence tumor immunity in complex ways that are not fully understood. In this study, we characterized a population of human differentiated effector CD4+ T cells that is defined by low levels of the interleukin (IL)-2 and IL-7 receptors (CD25−CD127−). We found that this cell population expands in patients with various types of cancer, including breast cancer, to represent 2% to 20% of total CD4+ blood T lymphocytes as compared with only 0.2% to 2% in healthy individuals. Notably, these CD25−CD127−CD4 T cells expressed effector markers such as CD244 and CD11b with low levels of CD27, contrasting with the memory phenotype dominating this population in healthy individuals. These cells did not cycle in patients, nor did they secrete IL-10 or IL-17, but instead displayed cytotoxic features. Moreover, they encompassed oligoclonal expansions paralleling an expansion of effector CD8+ T cells that included tumor antigen–specific T cells. During neoadjuvant chemotherapy in patients with breast cancer, we found that the increase in CD25−CD127− CD4+ T cells correlated with tumor regression. This observation suggested that CD4+ T cells included tumor antigen–specific cells, which may be generated by or participate in tumor regressions during chemotherapy. In summary, our results lend support to the hypothesis that CD4+ T cells are involved in human antitumor responses. Cancer Res; 74(8); 2204–16. ©2014 AACR.
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- 2014
10. Analysis of APC types involved in CD4 tolerance and regulatory T cell generation using reaggregated thymic organ cultures
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Sabrina Nabti, Lucia Guerri, Yvette Geraldo, Olivier Lantz, Isabelle Peguillet, and Virginie Premel
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Stromal cell ,Regulatory T cell ,Immunology ,Cell Culture Techniques ,Thymus Gland ,T-Lymphocytes, Regulatory ,Epithelium ,Negative selection ,Mice ,Fetus ,Antigens, CD ,medicine ,Immunology and Allergy ,Animals ,B-Lymphocytes ,Thymocytes ,biology ,Macrophages ,Dendritic Cells ,Cell biology ,Eosinophils ,Haematopoiesis ,Thymocyte ,medicine.anatomical_structure ,Self Tolerance ,Polyclonal antibodies ,Monoclonal ,T cell subset ,biology.protein ,Female ,Stromal Cells - Abstract
Tolerance to self-Ags is generated in the thymus. Both epithelial and hematopoietic thymic stromal cells play an active and essential role in this process. However, the role of each of the various stromal cell types remains unresolved. To our knowledge, we describe the first comparative analysis of several types of thymic hematopoietic stromal cells (THSCs) for their ability to induce CD4 tolerance to self, in parallel with the thymic epithelium. The THSCs—two types of conventional dendritic cells (cDCs), plasmacytoid dendritic cells, macrophages (MΦs), B lymphocytes, and eosinophils—were first characterized and quantified in adult mouse thymus. They were then examined in reaggregated thymic organ cultures containing mixtures of monoclonal and polyclonal thymocytes. This thymocyte mixture allows for the analysis of Ag-specific events while avoiding the extreme skewing frequently seen in purely monoclonal systems. Our data indicate that thymic epithelium alone is capable of promoting self-tolerance by eliminating autoreactive CD4 single-positive thymocytes and by supporting regulatory T cell (Treg) development. We also show that both non-Treg CD4 single-positive thymocytes and Tregs are efficiently deleted by the two populations of cDCs present in the thymus, as well as to a lesser extent by MΦs. Plasmacytoid dendritic cells, B lymphocytes, and eosinophils were not able to do so. Finally, cDCs were also the most efficient THSCs at supporting Treg development in the thymus, suggesting that although they may share some characteristics required for negative selection with MΦs, they do not share those required for the support of Treg development, making cDCs a unique cell subset in the thymus.
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- 2013
11. Age-Related Patterns in Human Myeloid Dendritic Cell Populations in People Exposed to Schistosoma haematobium Infection
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Nicholas Midzi, Olivier Lantz, Takafira Mduluza, Norman Nausch, François Trottein, Laura J. Appleby, Delphine Louis, Francisca Mutapi, Isobel Y. D. Chen, Isabelle Peguillet, and Claire D. Bourke
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Male ,Myeloid ,Helminth Infection ,Cohort Studies ,Schistosomiasis haematobia ,0302 clinical medicine ,Schistosomiasis ,Young adult ,Child ,Immune Response ,Schistosoma haematobium ,0303 health sciences ,education.field_of_study ,biology ,lcsh:Public aspects of medicine ,Age Factors ,Middle Aged ,Acquired immune system ,Flow Cytometry ,3. Good health ,medicine.anatomical_structure ,Infectious Diseases ,Child, Preschool ,Urinary Tract Infections ,Medicine ,Female ,Research Article ,Neglected Tropical Diseases ,Adult ,Zimbabwe ,lcsh:Arctic medicine. Tropical medicine ,Adolescent ,lcsh:RC955-962 ,Immune Cells ,Population ,Immunology ,Immunomodulation ,03 medical and health sciences ,Young Adult ,Immune system ,medicine ,Parasitic Diseases ,Animals ,Humans ,education ,Biology ,030304 developmental biology ,Schistosoma ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,Dendritic cell ,Dendritic Cells ,biology.organism_classification ,030215 immunology - Abstract
Background Urogenital schistosomiasis is caused by the helminth parasite Schistosoma haematobium. In high transmission areas, children acquire schistosome infection early in life with infection levels peaking in early childhood and subsequently declining in late childhood. This age-related infection profile is thought to result from the gradual development of protective acquired immunity. Age-related differences in schistosome-specific humoral and cellular responses have been reported from several field studies. However there has not yet been a systematic study of the age-related changes in human dendritic cells, the drivers of T cell polarisation. Methods Peripheral blood mononuclear cells were obtained from a cohort of 61 Zimbabwean aged 5–45 years with a S. haematobium prevalence of 47.5%. Two subsets of dendritic cells, myeloid and plasmacytoid dentritic cells (mDCs and pDCs), were analyzed by flow cytometry. Findings In this population, schistosome infection levels peaked in the youngest age group (5–9 years), and declined in late childhood and adulthood (10+ years). The proportions of both mDCs and pDCs varied with age. However, for mDCs the age profile depended on host infection status. In the youngest age group infected people had enhanced proportions of mDCs as well as lower levels of HLA-DR on mDCs than un-infected people. In the older age groups (10–13 and 14–45 years) infected people had lower proportions of mDCs compared to un-infected individuals, but no infection status-related differences were observed in their levels of HLA-DR. Moreover mDC proportions correlated with levels of schistosome-specific IgG, which can be associated with protective immunity. In contrast proportions of pDCs varied with host age, but not with infection status. Conclusions Our results show that dendritic cell proportions and activation in a human population living in schistosome-endemic areas vary with host age reflecting differences in cumulative history of exposure to schistosome infection., Author Summary A characteristic feature of most helminth infections is the convex age infection profile, where infection levels rise to peak in early childhood and decline in adulthood, a pattern thought to result from the development of protective acquired immunity. Thus, several investigations characterizing protective responses to inform vaccine research have focused on responses present in older people, who despite continued exposure to infection carry little or no infection. To date, such studies have identified key responses which are correlates of resistance. However, there is a paucity of information on cell types that are mediators rather than effectors of the immune responses. One such group where there are limited studies in human schistosome infections is dendritic cells which are important for the polarizations of CD4+ T cell responses. Therefore, we characterized the age profile of dendritic cells in Zimbabweans exposed to Schistosoma haematobium infection. We found an age-related pattern in the proportions of myeloid dendritic cells (a subset of dendritic cells) in this population. Furthermore, in the case myeloid dendritic cells, the age profile differed between schistosome infected and un-infected people. Thus our study suggests that activation and migration of myeloid dendritic cells also develop in an age-related pattern consistent with the cumulative history of exposure to schistosome parasites.
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- 2012
12. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells
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Delphine Louis, Nacer Serriari, Lionel Le Bourhis, Olivier Lantz, Emmanuel Martin, Isabelle Peguillet, Claire Soudais, Mathilde Dusseaux, Emmanuel Treiner, Virginie Premel, and Maud Milder
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Immunology ,Population ,Drug Resistance ,C-C chemokine receptor type 7 ,Mucosal associated invariant T cell ,C-C chemokine receptor type 6 ,Biology ,CD8-Positive T-Lymphocytes ,Biochemistry ,Xenobiotics ,Cell Movement ,Cytotoxic T cell ,Humans ,education ,Child ,Immunity, Mucosal ,Cells, Cultured ,education.field_of_study ,Interleukin-17 ,Infant, Newborn ,Cell Biology ,Hematology ,T lymphocyte ,Th1 Cells ,Fetal Blood ,Molecular biology ,Organ Specificity ,Receptors, Chemokine ,Interleukin 17 ,Interleukin-18 Receptor alpha Subunit ,CD8 ,NK Cell Lectin-Like Receptor Subfamily B - Abstract
Mucosal-associated invariant T (MAIT) cells are very abundant in humans and have antimicrobial specificity, but their functions remain unclear. MAIT cells are CD161hiIL-18Rα+ and either CD4−CD8− (DN) or CD8αβint T cells. We now show that they display an effector-memory phenotype (CD45RA−CD45RO+CD95hiCD62Llo), and their chemokine receptor expression pattern (CCR9intCCR7−CCR5hiCXCR6hiCCR6hi) indicates preferential homing to tissues and particularly the intestine and the liver. MAIT cells can represent up to 45% of the liver lymphocytes. They produce interferon-γ and Granzyme-B as well as high levels of interleukin-17 after phorbol myristate acetate + ionomycin stimulation. Most MAIT cells are noncycling cells (< 1% are Ki-67+) and express the multidrug resistance transporter (ABCB1). As expected from this phenotype, MAIT cells are more resistant to chemotherapy than other T-cell populations. These features might also allow MAIT cells to resist the xenobiotics potentially secreted by the gut bacteria. We also show that this population does not appear to have antiviral specificity and that CD8 MAIT cells include almost all the ABCB1+CD161hi CD8 T cells. Together with their already known abundance and antimicrobial specificity, the gut-liver homing characteristics, high expression of ABCB1, and ability to secrete interleukin-17 probably participate in the antibacterial properties of MAIT cells.
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- 2010
13. High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling
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Brigitte Gicquel, Jean-Philippe Carralot, Florence Levillain, Martine Gilleron, Jean Rauzier, Graham R. Stewart, Carlos Martin, Mi-Seon Jang, Olivier Neyrolles, Gerald Larrouy-Maumus, Denis Philippe Cedric Fenistein, Thierry Christophe, Jichan Jang, Rachel Shrimpton, Jesús Gonzalo-Asensio, Yannick Poquet, Fanny Anne Ewann, Auguste Genovesio, Seijin Park, Germain Puzo, Isabelle Peguillet, Roland Brosch, Priscille Brodin, Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP), Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), University of Surrey (UNIS), University of Zaragoza - Universidad de Zaragoza [Zaragoza], This work was supported by INSERM, CNRS, Fondation pour la Recherche Medicale, Institut Pasteur Paris (incl. Programme Transversal de Recherche nr 253), Institut Pasteur Korea, and the European Community (TB-MACS, Grant nr LSHP-CT-2006-037732, TB-VIR, Grant nr 200973, and EU-FP7 NEWTBVAC project, Grant nr 241745) and the Korea Research Foundation Grant (K20802001409-09B1300-03700). P.B. is a fellow of an INSERM-Avenir fellowship, O.N. is a fellow of a CNRS-ATIP fellowship., European Project: 200973,EC:FP7:HEALTH,FP7-HEALTH-2007-A,TB-VIR(2008), European Project: 241745,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,NEWTBVAC(2010), European Project: 38948,TB-MACS, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genovesio, Auguste, Mycobacterium tuberculosis W-Beijing genetic diversity and differential virulence and host immune responses - TB-VIR - - EC:FP7:HEALTH2008-04-01 - 2011-03-31 - 200973 - VALID, Discovery and preclinical development of new generation tuberculosis vaccines - NEWTBVAC - - EC:FP7:HEALTH2010-01-01 - 2014-02-28 - 241745 - VALID, Identification and characterization of Mycobacterium tuberculosis virulence genes involved in macrophage parasitism - TB-MACS - 38948 - OLD, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Institut Pasteur [Paris]
- Subjects
Lipopolysaccharides ,Magnetic Resonance Spectroscopy ,[SDV]Life Sciences [q-bio] ,Mutant ,Infectious Diseases/Bacterial Infections ,Mice ,Phagosomes ,Biology (General) ,ComputingMilieux_MISCELLANEOUS ,Phagosome ,0303 health sciences ,Mice, Inbred BALB C ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,Female ,Microbiology/Cellular Microbiology and Pathogenesis ,Functional genomics ,Intracellular ,Research Article ,QH301-705.5 ,Phagocytosis ,Immunology ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Microbiology ,Mycobacterium tuberculosis ,03 medical and health sciences ,Virology ,Phagosome maturation ,Genetics ,Animals ,Tuberculosis ,Molecular Biology ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,030304 developmental biology ,030306 microbiology ,Intracellular parasite ,Infectious Diseases/Respiratory Infections ,Macrophages ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,RC581-607 ,biology.organism_classification ,Mice, Inbred C57BL ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mutation ,Parasitology ,Immunologic diseases. Allergy ,Glycolipids - Abstract
The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis of over 11,000 Mycobacterium tuberculosis mutants. This very stringent assay makes use of fluorescent staining for intracellular acidic compartments, and automated confocal microscopy to quantitatively determine the intracellular localization of M. tuberculosis. We characterised the ten mutants that traffic most frequently into acidified compartments early after phagocytosis, suggesting that they had lost their ability to arrest phagosomal maturation. Molecular analysis of these mutants revealed mainly disruptions in genes involved in cell envelope biogenesis (fadD28), the ESX-1 secretion system (espL/Rv3880), molybdopterin biosynthesis (moaC1 and moaD1), as well as in genes from a novel locus, Rv1503c-Rv1506c. Most interestingly, the mutants in Rv1503c and Rv1506c were perturbed in the biosynthesis of acyltrehalose-containing glycolipids. Our results suggest that such glycolipids indeed play a critical role in the early intracellular fate of the tubercle bacillus. The unbiased approach developed here can be easily adapted for functional genomics study of intracellular pathogens, together with focused discovery of new anti-microbials., Author Summary One of the major virulence mechanisms of the tuberculosis bacillus, Mycobacterium tuberculosis, is its ability to resist killing by phagocytic cells of the host immune system, namely the macrophages. Macrophages degrade invading microbes by engulfment inside a vacuole, or phagosome, that progressively acidifies and accumulates hydrolytic properties. M. tuberculosis has the unique ability to block phagosome maturation and acidification. To identify mycobacterial genes involved in phagosome maturation arrest, we developed a novel high-throughput technology based on automated confocal microscopy. We screened a library containing over 11,000 M. tuberculosis mutants, and we could identify 10 mutants that had lost their ability to resist phagosome acidification. Genetic characterization of these mutants revealed that they carried lesions in genes involved in various cell processes, including biogenesis of the cell envelope. In particular, two independent mutants in the same genetic locus showed altered production of two lipids, namely diacyltrehalose (DAT) and sulfoglycolipid (SGL). In vitro experiments showed that SGL can indeed influence phagosome maturation. Our study unravels the role of novel lipid molecules in mycobacterial intracellular parasitism; our approach may be useful to identify virulence genes in other intracellular pathogens, and to identify novel antimicrobials.
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- 2010
14. Anti-microbial activity of Mucosal Associated Invariant T cells
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Eva Lévy, Vanina Meyssonnier, Claire Soudais, Lionel Le Bourhis, Béatrice Riteau, Livine Duban, Maxime Coré, Isabelle Peguillet, Mathilde Dusseaux, Amélie Guihot, Olivier Lantz, Delphine Robert, Charlotte Ngo, Nathalie Froux, Shouxiong Huang, Emmanuel Martin, Virginie Premel, Martin Rottman, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), Département de chirurgie, Institut Curie [Paris], Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Infection et inflammation (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Peer, Hal, Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie, Unité de recherche Virologie et Immunologie Moléculaires (VIM), Physiopathologie et diagnostic des infections microbiennes (EPIM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Curie, Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Transgenèse et archivage d'animaux modèles ( TAAM ), Centre National de la Recherche Scientifique ( CNRS ), INSTITUT CURIE, Unité de recherche Virologie et Immunologie Moléculaires ( VIM ), Institut National de la Recherche Agronomique ( INRA ), Physiopathologie et diagnostic des infections microbiennes ( EPIM ), and Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ )
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T-Lymphocytes ,[SDV]Life Sciences [q-bio] ,Immunology ,Receptors, Antigen, T-Cell ,T cells ,Antigen-Presenting Cells ,Mice, Transgenic ,Mucosal associated invariant T cell ,Lymphocyte Activation ,Major histocompatibility complex ,Virus ,Microbiology ,Minor Histocompatibility Antigens ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,Minor histocompatibility antigen ,Animals ,Humans ,Immunology and Allergy ,Immunity, Mucosal ,030304 developmental biology ,Mice, Knockout ,Innate immunity ,0303 health sciences ,Innate immune system ,biology ,Histocompatibility Antigens Class I ,T-cell receptor ,Bacterial Infections ,Virology ,Immunity, Innate ,3. Good health ,[SDV] Life Sciences [q-bio] ,biology.protein ,Mucosal immunology ,Immunologic Memory ,030215 immunology - Abstract
Mucosal-associated invariant T lymphocytes (MAIT lymphocytes) are characterized by two evolutionarily conserved features: an invariant T cell antigen receptor (TCR) alpha-chain and restriction by the major histocompatibility complex (MHC)-related protein MR1. Here we show that MAIT cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. This activation required cognate interaction between the invariant TCR and MR1, which can present a bacteria-derived ligand. In humans, we observed considerably fewer MAIT cells in blood from patients with bacterial infections such as tuberculosis. In the mouse, MAIT cells protected against infection by Mycobacterium abscessus or Escherichia coli. Thus, MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection.
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- 2010
15. Establishment and characterization of a panel of human uveal melanoma xenografts derived from primary and/or metastatic tumors
- Author
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Sergio Roman-Roman, Jérôme Couturier, Marie-Hélène Donnadieu, Fariba Nemati, Corine Plancher, Bernard Asselain, Didier Decaudin, Isabelle Peguillet, Delphine Robert, Xavier Sastre-Garau, Laurence Desjardins, Cécile Reyes, Olivier Lantz, Marie-Andrée Bessard, Sophie Piperno-Neumann, Simon Saule, David Gentien, Ahmed Dahmani, Cécile Laurent, Emmanuel Barillot, and Pascale Mariani
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Male ,Uveal Neoplasms ,Cancer Research ,Pathology ,medicine.medical_specialty ,Mice, SCID ,Polymorphism, Single Nucleotide ,Nitrosourea Compounds ,Metastasis ,Mice ,Organophosphorus Compounds ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Biomarkers, Tumor ,Temozolomide ,Tumor Cells, Cultured ,Animals ,Humans ,Neoplasm Metastasis ,Melanoma ,In Situ Hybridization, Fluorescence ,Oligonucleotide Array Sequence Analysis ,business.industry ,Gene Expression Profiling ,Cancer ,Middle Aged ,medicine.disease ,Xenograft Model Antitumor Assays ,Tumor antigen ,Transplantation ,Dacarbazine ,Oncology ,Cancer research ,Fotemustine ,Female ,business ,medicine.drug ,Tumor Graft - Abstract
Purpose: Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice. Experimental Design: Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma. Results: Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents. Conclusions: Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments. Clin Cancer Res; 16(8); 2352–62. ©2010 AACR.
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- 2010
16. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression
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Isabelle Peguillet, Olivier Lantz, José Mordoh, Erika Von Euw, Michele Bianchini, Estrella Mariel Levy, Rosa Wainstok, Maria Marcela Barrio, Cassian Yee, Matias Chacon, David Furman, Abraham Kohan, and Alejandra Vellice
- Subjects
Adult ,Male ,Adolescent ,Genotype ,lcsh:Medicine ,Apoptosis ,chemical and pharmacologic phenomena ,Lymphocyte proliferation ,Lymphocyte Activation ,Cancer Vaccines ,Transplantation, Autologous ,General Biochemistry, Genetics and Molecular Biology ,Necrosis ,Immune system ,Phagocytosis ,Predictive Value of Tests ,Humans ,Medicine ,Hypersensitivity, Delayed ,Promoter Regions, Genetic ,Melanoma ,Neoplasm Staging ,Medicine(all) ,Polymorphism, Genetic ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,Patient Selection ,Research ,Monocyte ,lcsh:R ,hemic and immune systems ,Dendritic Cells ,General Medicine ,Dendritic cell ,Middle Aged ,medicine.disease ,digestive system diseases ,Interleukin-10 ,Interleukin 10 ,medicine.anatomical_structure ,Granulocyte macrophage colony-stimulating factor ,Immunology ,Disease Progression ,Female ,Cancer vaccine ,business ,medicine.drug - Abstract
BackgroundSixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec), to evaluate toxicity and immune responses. Also, IL-10 1082 genotype was analyzed in an effort to predict disease progression.MethodsPBMC were obtained after leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines each with 5, 10, 15, or 20 × 106DC/Apo-Nec cell per vaccine, two weeks apart. Immune responses were measured by ELISpot and tetramer analysis. Il-10 genotype was measured by PCR and corroborated by IL-10 production by stimulated PBMC.ResultsImmature DCs efficiently phagocytosed melanoma Apo-Nec cells and matured after phagocytosis as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II, and 75.2 ± 16% reduction in Dextran-FITC endocytosis. CCR7 was also up-regulated upon Apo-Nec uptake in DCs from all patients, and accordingly DC/Apo-Nec cells were able to migratein vitrotoward MIP-3 beta. The vaccine was well tolerated in all patients. The DTH score increased significantly in all patients after the first vaccination (Mann-Whitney Test, p < 0.05). The presence of CD8+T lymphocytes specific to gp100 and Melan A/MART-1 Ags was determined by ELISpot and tetramer analysis in five HLA-A*0201 patients before and after vaccination; one patient had stable elevated levels before and after vaccination; two increased their CD8 + levels, one had stable moderate and one had negligible levels. The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lowerin vitroIL-10 production by stimulated PBMC, and faster melanoma progression after lymph nodes surgery (p = 0.04). With a mean follow-up of 49.5 months post-surgery, one stage IIC patient and 7/8 stage III patients remain NED but 7/7 stage IV patients have progressed.ConclusionWe conclude that DC/Apo-Nec vaccine is safe, well tolerated and it may induce specific immunity against melanoma Ags. Patients with a low-producing IL-10 polymorphism appear to have a worst prognosis.Trial registrationClinicaltrials.gov (NHI) NCT00515983
- Published
- 2008
17. Skin carcinoma arising from donor cells in a kidney transplant recipient
- Author
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Edgardo D. Carosella, Sylvie Euvrard, Caroline Le Danff, Jean Kanitakis, Kiarash Khosrotehrani, Isabelle Peguillet, Olivier Lantz, and Selim Aractingi
- Subjects
Keratinocytes ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Bowen's Disease ,Biology ,Skin Diseases ,Cell Fusion ,Immunoenzyme Techniques ,Immune system ,medicine ,Carcinoma ,Humans ,Transplantation, Homologous ,Basal cell carcinoma ,Kidney transplantation ,In Situ Hybridization, Fluorescence ,Chromosomes, Human, X ,Chromosomes, Human, Y ,Reverse Transcriptase Polymerase Chain Reaction ,Stem Cells ,Actinic keratosis ,Cell Differentiation ,Keratosis ,medicine.disease ,Kidney Transplantation ,Tissue Donors ,Keratoacanthoma ,Oncology ,Carcinoma, Basal Cell ,Karyotyping ,Carcinoma, Squamous Cell ,Keratins ,Female ,Skin cancer ,Stem cell ,Skin Carcinoma - Abstract
The incidence of skin cancer is increased in transplant recipients. UV radiation, papillomaviruses, and immunosuppression participate in the pathogenesis of these tumors. In addition, donor cells may leave the grafted organ, reach peripheral tissues and either induce immune phenomena or possibly take part in tissue remodeling. Herein, we investigated the possible involvement of donor cells in the development of skin tumors in kidney allograft recipients. We analyzed a series of 48 malignant and benign cutaneous tumors developing in 14 females who had been grafted with a male kidney. The number of male cells was measured on microdissected material by quantitative PCR for Y chromosome. In the samples with high levels of male cells, fluorescent in situ hybridization (FISH) with X and Y probes and/or immuno-FISH with anticytokeratin antibodies were carried out. Male cells were detected in 5/15 squamous cell carcinomas and Bowen disease (range 4-180 copies), 3/5 basal cell carcinomas (91-645), 6/11 actinic keratosis (7-102), 2/4 keratoacanthoma (22-41), and 2/5 benign cutaneous lesions (14-55). In a basal cell carcinoma specimen with a high number of male cells, FISH showed that most cells within the tumoral buds were XY. In this lesion, immuno-FISH showed the presence of XY cytokeratin-positive cells indicating that the tumor nests contained male keratinocytes. In contrast, in other female transplants, male cells present in the tumors were not epithelial. In conclusion, stem cells originating from a grafted kidney may migrate to the skin, differentiate, or fuse as keratinocytes that could, rarely, undergo cancer transformation.
- Published
- 2005
18. Anti-bacterial Function of Mucosal Associated Invariant T Cells
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Maxime Coré, Amélie Guihot, Mathilde Dusseaux, Charlotte Ngo, Claire Soudais, Olivier Lantz, Martin Rottman, Emmanuel Martin, Delphine Robert, Virginie Premel, Vanessa Meyssonier, Isabelle Peguillet, and Lionel Le Bourhis
- Subjects
Chemistry ,Immunology ,Immunology and Allergy ,Mucosal associated invariant T cell ,Anti bacterial ,Molecular biology ,Function (biology) - Published
- 2010
19. Quantification of porcine cytokine gene expression using RT-PCR, a homologous internal control and chemiluminescence for microplate detection
- Author
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Albina Emmanuel, Isabelle Peguillet, Vinciane Dufour, Olivier Lantz, Karine Morvilliers, Claire Arnauld, and André Jestin
- Subjects
Swine ,medicine.medical_treatment ,Immunology ,Molecular Sequence Data ,Biology ,Peripheral blood mononuclear cell ,Sensitivity and Specificity ,law.invention ,Interferon ,law ,medicine ,Immunology and Allergy ,Animals ,RNA, Messenger ,Polymerase chain reaction ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Interleukin ,Glyceraldehyde-3-Phosphate Dehydrogenases ,Amplicon ,Virology ,Molecular biology ,Housekeeping gene ,Real-time polymerase chain reaction ,Cytokine ,Luminescent Measurements ,Cytokines ,medicine.drug - Abstract
The polymerase chain reaction (PCR) has proved to be a sensitive and versatile method for the analysis of human and murine cytokine mRNA expression. This paper describes for the first time a reverse transcription-polymerase chain reaction (RT-PCR) at end-point for the quantification of five porcine cytokines: interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-10 and IL-18. The main features of the methodology are: (1) a unique RT for all quantifications, (2) the addition of homologous DNA internal controls (IC) of equal length to the corresponding cytokine and consequently co-amplification of the target cytokine and the IC with equivalent efficacy, (3) PCR and detection of amplicons for all cytokines simultaneously, (4) cytokine quantification in relation to a housekeeping gene control (glyceraldehyde-3-phosphate dehydrogenase, GAPDH), (5) detection of the amplicons by enzyme linked immunosorbent assay (ELISA) using a chemiluminescent substrate with high sensitivity and wide dynamic range, (6) automation of the detection system for analysis of a large number of samples. This highly sensitive quantitative RT-PCR assay (able to detect 100–200 cytokines mRNA copies/75×103 cells) was validated on peripheral blood mononuclear cells (PBMC) from pigs infected or not with pseudorabies virus (PRV), re-stimulated in vitro by a mitogen or antigens.
- Published
- 1999
20. Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene expression after 1 year of highly active antiretroviral therapy
- Author
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Frédéric Martinon, Isabelle Peguillet, Jean-François Delfraissy, Christian Michelet, Philippe Lefebvre, Yassine Taoufik, Olivier Lantz, Cécile Goujard, and Jean-Gérard Guillet
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Chemokine ,Receptors, CXCR4 ,Receptors, CCR5 ,Anti-HIV Agents ,medicine.medical_treatment ,Receptors, CCR3 ,Immunology ,Gene Expression ,HIV Infections ,Zidovudine ,Chemokine receptor ,Interferon-gamma ,medicine ,Immunology and Allergy ,Humans ,Longitudinal Studies ,RNA, Messenger ,Saquinavir ,Interleukin-13 ,Ritonavir ,biology ,Receptors, Interleukin-12 ,Lamivudine ,HIV Protease Inhibitors ,Receptors, Interleukin ,Chemokine Receptor Gene ,Virology ,Interleukin-10 ,Infectious Diseases ,Cytokine ,biology.protein ,Cytokines ,Interleukin-2 ,Reverse Transcriptase Inhibitors ,Female ,Receptors, Chemokine ,Interleukin-4 ,CD8 ,medicine.drug - Abstract
OBJECTIVES To examine T-cell repertoire modifications, the evolution of T-helper (TH)1/TH2 cytokine imbalance and modifications in chemokine receptor expression when the viral load is decreased by 2-3 log10 copies/ml under highly active antiretroviral therapy (HAART). DESIGN Sixteen patients previously treated with zidovudine and lamivudine, with CD4 cells below 300 x 10(6)/l and viraemia above 30000 copies/ml were treated by saquinavir and ritonavir together with both reverse transcriptase (RT) inhibitors (ANRS 069 trial). T-cell repertoire, chemokine receptor and lymphokine expression were studied from peripheral blood mononuclear cells sampled at weeks 0, 24 and 48. METHODS T-cell repertoire study was carried out using the Immunoscope method. Interleukin (IL)-12 receptor beta2, CC-chemokine receptor (CCR)-3, CXC-chemokine receptor-4 and CCR-5 expression in CD4+ cells was measured by kinetic quantitative PCR and IL-2, IL-4, IL-10, IL-13, interferon (IFN)-gamma were measured using a quantitative RT-PCR assay with homologous internal standards. RESULTS Repertoire alterations were more frequent in CD4- than in CD4+ cells and persisted despite undetectable viraemia. Increased CCR-3 expression and spontaneous IFN-gamma as well as mitogenic induced IL-13 were observed at baseline and decreased slightly under HAART. CONCLUSION The CD8+ cell repertoire alterations were profound, whereas the CD4+ cell alterations were moderate and both persisted unchanged under HAART. The TH1/TH2 imbalance was more related to TH2 over-expression than to TH1 deficiency and persisted for at least 1 year under HAART.
- Published
- 1999
21. Effect of Highly Active Antiretroviral Therapy on Expression of Interleukin-10 and Interleukin-12 in HIV-Infected Patients
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Yassine Taoufik, Marie-Ghislaine de Goër, Isabelle Peguillet, Brigitte Gubler, Aldo Trylesinski, Jean François Delfraissy, Olivier Lantz, and Marion Lambert
- Subjects
Anti-HIV Agents ,HIV Infections ,Virus ,Acquired immunodeficiency syndrome (AIDS) ,Immunopathology ,Antiretroviral Therapy, Highly Active ,medicine ,Humans ,Pharmacology (medical) ,RNA, Messenger ,Sida ,biology ,business.industry ,Viral Load ,biology.organism_classification ,medicine.disease ,Virology ,Interleukin-12 ,Interleukin-10 ,Interleukin 10 ,Infectious Diseases ,Gene Expression Regulation ,Lentivirus ,Immunology ,Interleukin 12 ,HIV-1 ,Viral disease ,business - Published
- 2001
22. Erratum: Corrigendum: Antimicrobial activity of mucosal-associated invariant T cells
- Author
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Claire Soudais, Mathilde Dusseaux, Delphine Robert, Martin Rottman, Amélie Guihot, Livine Duban, Nathalie Froux, Isabelle Peguillet, Eva Lévy, Béatrice Riteau, Lionel Le Bourhis, Olivier Lantz, Charlotte Ngo, Virginie Premel, Maxime Coré, Emmanuel Martin, and Vanina Meyssonnier
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business.industry ,Immunology ,Immunology and Allergy ,Medicine ,Mucosal associated invariant T cell ,Antimicrobial ,business - Abstract
Nat. Immunol. 11, 701–708 (2010); published online 27 June 2010; corrected after print 13 August 2010 In the version of this article initially published, the author Shouxiong Huang (Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA) was not included. This authorshould be listed as author 15 (and affiliation 8).
- Published
- 2010
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