期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 219, 期 11, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20220650
关键词
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资金
- Deutsche Forschungsgemeinschaft [390857198]
- Biogen - Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology
- Gemeinnutzige Hertie Stiftung
- National Association of the German MS Society
- Carmen Ellinger Foundation
- Association Verein zur Therapieforschung
- Dr. Leopold and Carmen Ellinger Foundation
- [445569437]
- [CRC128]
The EBV-specific T cell receptor repertoire is broader in multiple sclerosis patients, indicating an ongoing immune response to Epstein-Barr virus, which might provide clues for multiple sclerosis pathogenesis and future therapeutic approaches.
The EBV-specific T cell receptor repertoire is broader in multiple sclerosis patients, even in diseased siblings of discordant monozygotic twin pairs, indicating an ongoing immune response to Epstein-Barr virus in multiple sclerosis patients, which might hold clues for multiple sclerosis pathogenesis and future therapeutic or preventive avenues. 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 beta chain (TCR beta) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCR beta sequences. We detected more MHC-I-restricted EBV-specific TCR beta 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 beta- 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.
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