Ontology highlight
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 V? 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 V? 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.
SUBMITTER: Salou M
PROVIDER: S-EPMC4479522 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Salou Marion M Garcia Alexandra A Michel Laure L Gainche-Salmon Anne A Loussouarn Delphine D Nicol Bryan B Guillot Flora F Hulin Philippe P Nedellec Steven S Baron Daniel D Ramstein Gérard G Soulillou Jean-Paul JP Brouard Sophie S Nicot Arnaud B AB Degauque Nicolas N Laplaud David A DA
Annals of clinical and translational neurology 20150428 6
<h4>Objective</h4>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.<h4>Methods</h4>For the first time, TCR Vβ repertoire from paired blood (purified CD8(+) and CD4(+) T cells), ...[more]