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Journal Articles Annals of Clinical and Translational Neurology Year : 2015

Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis

Delphine Loussouarn
  • Function : Author

Abstract

Objective In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8+ T cells. These clones have been assumed – but never demonstrated – to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8+ T cells in the disease. Methods For the first time, TCR Vβ repertoire from paired blood (purified CD8+ and CD4+ T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8+ T cells were characterized by fluorescent staining. Results TCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8+ T cells. In parallel, we showed that blood oligoclonal CD8+ T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B.

Dates and versions

hal-01200787 , version 1 (17-09-2015)

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Marion Salou, Alexandra Garcia, Laure Michel, Anne Gainche-Salmon, Delphine Loussouarn, et al.. Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis. Annals of Clinical and Translational Neurology, 2015, pp.2(6): 609-622. ⟨10.1002/acn3.199⟩. ⟨hal-01200787⟩
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