Expanded CD 8 T‐cell sharing between periphery and CNS in multiple sclerosis
M Salou, A Garcia, L Michel… - Annals of clinical …, 2015 - Wiley Online Library
M Salou, A Garcia, L Michel, A Gainche‐Salmon, D Loussouarn, B Nicol, F Guillot, P Hulin…
Annals of clinical and translational neurology, 2015•Wiley Online LibraryObjective In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid
(CSF), and blood display TCR clonal expansions of CD 8+ 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 CD 8+ T
cells in the disease. Methods For the first time, TCR Vβ repertoire from paired blood (purified
CD 8+ and CD 4+ T cells), CSF and CNS (22 lesions, various inflammatory and …
(CSF), and blood display TCR clonal expansions of CD 8+ 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 CD 8+ T
cells in the disease. Methods For the first time, TCR Vβ repertoire from paired blood (purified
CD 8+ and CD 4+ T cells), CSF and CNS (22 lesions, various inflammatory and …
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.
Interpretation
This study highlights the predominant implication of CD8+ T cells in MS pathophysiology and demonstrates that potentially aggressive CD8+ T cells can be easily identified and characterized from blood and CSF samples.
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