Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients.
Multiple sclerosis is a chronic inflammatory demyelinating disease of the CNS. Although the aetiology of multiple sclerosis is still unknown, it is widely believed that T cells play a central role in its pathogenesis. To identify and characterize disease-relevant T cells, we analysed CD4+ and CD8+ T cells freshly isolated from the CSF and peripheral blood of 36 multiple sclerosis patients for their T-cell receptor variable beta (TCRBV) chain repertoire. In most patients, we found significant overexpression of individual TCRBV chains on CD8+ T cells from CSF compared with peripheral blood. In contrast, only a few multiple sclerosis patients showed differences between the two compartments in TCRBV expression on CD4+ T cells. The overexpression of specific TCRBV chains on CD8+ T cells was found to be stable over several months in selected patients and involved mainly T cells with a memory phenotype. In two patients studied, individual TCRBV chain overexpression was found to be caused by the expansion of T cell populations with identical or highly similar rearranged T-cell receptor beta- and alpha-chain sequences, which were not found among peripheral blood CD8+ T cells. Our findings demonstrate selective enrichment of memory CD8+ T cells in the CSF of multiple sclerosis patients, suggesting a role for these CD8+ T cells in the pathogenesis of multiple sclerosis. Our study provides a basis for future trials to identify disease-associated antigens and disease pathogenesis in multiple sclerosis.
Jacobsen
Marc
M
Clinical Neuroimmunology Group, Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8, 35033 Marburg, Germany.
Cepok
Sabine
S
Quak
Elfriede
E
Happel
Michael
M
Gaber
Rami
R
Ziegler
Andreas
A
Schock
Sabine
S
Oertel
Wolfgang H
WH
Sommer
Norbert
N
Hemmer
Bernhard
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology*
D000954:Antigens, Surface; D016693:Receptors, Antigen, T-Cell, alpha-beta