Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis - Université Toulouse III - Paul Sabatier - Toulouse INP Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2022

Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis

Rachel Gittelman
Florian Rubelt
Catarina Raposo
Florence Bucciarelli
Heidi Chapman
Ian Kaplan
David Brassat
Hartmut Wekerle
Martin Kerschensteiner
Reinhard Hohlfeld
Roland Liblau
Nicholas Schwab

Résumé

Epstein–Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen–specific TCRβ sequences. We detected more MHC-I–restricted EBV-specific TCRβ sequences in MS patients. Differences in genetics or upbringing could be excluded by validation in monozygotic twin pairs discordant for MS. Anti–VLA-4 treatment amplified this observation, while interferon β– or anti-CD20 treatment did not modulate EBV-specific T cell occurrence. In healthy individuals, EBV-specific CD8+ T cells were of an effector-memory phenotype in peripheral blood and cerebrospinal fluid. In MS patients, cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS.
Fichier principal
Vignette du fichier
SCHNEIDER-HOHENDORF-2022.pdf (3.05 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04076332 , version 1 (20-04-2023)

Identifiants

Citer

Tilman Schneider-Hohendorf, Lisa Ann Gerdes, Béatrice Pignolet, Rachel Gittelman, Patrick Ostkamp, et al.. Broader Epstein–Barr virus–specific T cell receptor repertoire in patients with multiple sclerosis. Journal of Experimental Medicine, 2022, 219 (11), ⟨10.1084/jem.20220650⟩. ⟨hal-04076332⟩
5 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More