Polyclonal expansion of TCR Vbeta 21.3 + CD4 + and CD8 + T cells is a hallmark of Multisystem Inflammatory Syndrome in Children.

Autor:	Moreews M; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Le Gouge K; Sorbonne Université, UPMC Univ Paris 06, INSERM UMRS 959, Immunology Immunopathology-Immunotherapy (i3), Paris, France., Khaldi-Plassart S; (RAISE), France; Pediatric Nephrology, Rheumatology, Dermatology Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon.; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in children., Pescarmona R; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in children.; Immunology Laboratory, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite., Mathieu AL; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France. alexandre.belot@chu-lyon.fr., Malcus C; Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France.; EA 7426 'Pathophysiology of Injury-Induced Immunosuppression' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, 69003, Lyon, France., Djebali S; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Bellomo A; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Dauwalder O; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, F-69004, Lyon, France., Perret M; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Immunology Laboratory, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite., Villard M; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Immunology Laboratory, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite., Chopin E; Cellular Biotechnology Department and Biobank, Hospices Civils de Lyon, Lyon, France., Rouvet I; Cellular Biotechnology Department and Biobank, Hospices Civils de Lyon, Lyon, France., Vandenesh F; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, F-69004, Lyon, France., Dupieux C; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, F-69004, Lyon, France., Pouyau R; Réanimation Pédiatrique Hôpital Femme-Mère-Enfant Hospices Civils de Lyon, Bron, France., Teyssedre S; Réanimation Pédiatrique Hôpital Femme-Mère-Enfant Hospices Civils de Lyon, Bron, France., Guerder M; Réanimation Pédiatrique Hôpital Femme-Mère-Enfant Hospices Civils de Lyon, Bron, France., Louazon T; Service de pédiatrie, Centre Hospitalier de Valence, France., Moulin-Zinsch A; Unité medico-chirurgicale des cardiopathies congénitales, hôpital Louis-Pradel, hospices civils de Lyon, 69677 Bron, France., Duperril M; Pediatric intensive care unit - University hospital of Saint-Étienne, France., Patural H; Pediatric intensive care unit - University hospital of Saint-Étienne, France.; U1059 INSERM - SAINBIOSE - DVH - Université de Saint-Étienne - 42055, France., Giovannini-Chami L; Pediatric Pulmonology and Allergology Department, Hôpitaux pédiatriques de Nice CHU-Lenval, Nice, France.; Université Côte d'Azur, France., Portefaix A; Center of Clinical Investigation, Lyon University Hospital, Bron, France., Kassai B; Center of Clinical Investigation, Lyon University Hospital, Bron, France., Venet F; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France., Monneret G; Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France.; EA 7426 'Pathophysiology of Injury-Induced Immunosuppression' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, 69003, Lyon, France., Lombard C; Immunology Laboratory, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite., Flodrops H; Service de Pédiatrie, Groupe Hospitalier Sud Réunion, CHU de La Réunion, Saint Pierre, La Réunion, France., De Guillebon JM; Service de Néphrologie, Rhumatologie pédiatrique, Hôpitaux pédiatriques de Nice CHU-Lenval, Nice, France., Bajolle F; Hôpital Necker Enfants Malades, Centre de référence M3C, AP-HP, Paris, France., Launay V; Urgences pédiatriques, Hôpital femme Mère Enfant, Hospices Civils de Lyon, Bron, France., Bastard P; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France., Zhang SY; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Dubois V; EFS Auvergne Rhône Alpes, laboratoire Histocompatibilité, 111, rue Elisée-Reclus, 69150 Décines, France., Thaunat O; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; EFS Auvergne Rhône Alpes, laboratoire Histocompatibilité, 111, rue Elisée-Reclus, 69150 Décines, France.; Department of Transplantation, Nephrology and Clinical Immunology, Edouard Herriot University Hospital, Lyon, France.; Lyon-Est Medical Faculty, Claude Bernard University (Lyon 1), 8, avenue Rockfeller, 69373, Lyon, France., Richard JC; Médecine Intensive-Réanimation, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.; Lyon University, France., Mezidi M; Médecine Intensive-Réanimation, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.; Lyon University, France., Allatif O; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Saker K; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Laboratoire de Virologie, Institut des Agents Infectieux, Laboratoire associé au Centre National de Référence des virus des infections respiratoires, Hospices Civils de Lyon, Lyon, France., Dreux M; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Abel L; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Casanova JL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.; University of Paris, Imagine Institute, Paris, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Howard Hughes Medical Institute, NY, USA., Marvel J; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Trouillet-Assant S; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.; Laboratoire de Virologie, Institut des Agents Infectieux, Laboratoire associé au Centre National de Référence des virus des infections respiratoires, Hospices Civils de Lyon, Lyon, France., Klatzmann D; Sorbonne Université, UPMC Univ Paris 06, INSERM UMRS 959, Immunology Immunopathology-Immunotherapy (i3), Paris, France.; Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Biotherapy and Département Hospitalo-Universitaire Inflammation-Immunopathology-Biotherapy (i2B), Paris, France., Walzer T; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France., Mariotti-Ferrandiz E; Sorbonne Université, UPMC Univ Paris 06, INSERM UMRS 959, Immunology Immunopathology-Immunotherapy (i3), Paris, France.; Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Biotherapy and Département Hospitalo-Universitaire Inflammation-Immunopathology-Biotherapy (i2B), Paris, France., Javouhey E; EA 7426 'Pathophysiology of Injury-Induced Immunosuppression' (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, 69003, Lyon, France.; Réanimation Pédiatrique Hôpital Femme-Mère-Enfant Hospices Civils de Lyon, Bron, France., Belot A; CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard, Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France. alexandre.belot@chu-lyon.fr.; Hospices Civils de Lyon, Edouard Herriot Hospital, Immunology Laboratory, 69437 Lyon, France.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2021 May 25; Vol. 6 (59).
DOI:	10.1126/sciimmunol.abh1516
Abstrakt:	Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vβ21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro . Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19. (Copyright © 2021, American Association for the Advancement of Science.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu