Format

Send to

Choose Destination
Ann Clin Transl Neurol. 2015 Jun;2(6):609-22. doi: 10.1002/acn3.199. Epub 2015 Apr 28.

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

Author information

1
INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France.
2
INSERM, UMR 1064 Nantes, F-44093, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
3
INSERM, UMR 1064 Nantes, F-44093, France ; Neurology Department, Nantes Hospital Nantes, F-44093, France.
4
INSERM, UMR 1064 Nantes, F-44093, France.
5
Pathology Department, Nantes Hospital Nantes, F-44093, France.
6
SFR François Bonamy, Cellular and Tissue Imaging Core Facility (MicroPICell) Nantes, F-44093, France.
7
INSERM, UMR 1064 Nantes, F-44093, France ; Medicine Department, Nantes University Nantes, F-44035, France ; Nantes Hospital, ITUN Nantes, F-44093, France.
8
LINA UMR6241, Nantes University Nantes, F-44093, France.
9
INSERM, UMR 1064 Nantes, F-44093, France ; Neurology Department, Nantes Hospital Nantes, F-44093, France ; INSERM 004, Centre d'Investigation Clinique Nantes, F-44093, France.

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.

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.

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center