title: Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients.
abstract: 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.
authors.affiliation: Clinical Neuroimmunology Group, Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8, 35033 Marburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Jacobsen
authors.forename: Sabine
authors.initials: S
authors.lastname: Cepok
authors.forename: Elfriede
authors.initials: E
authors.lastname: Quak
authors.forename: Michael
authors.initials: M
authors.lastname: Happel
authors.forename: Rami
authors.initials: R
authors.lastname: Gaber
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Sabine
authors.initials: S
authors.lastname: Schock
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Norbert
authors.initials: N
authors.lastname: Sommer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
mesh_terms: 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*
chemical_list: D000954:Antigens, Surface; D016693:Receptors, Antigen, T-Cell, alpha-beta