Brain 2002 Mar;125(Pt 3):538-50
Jacobsen M, Cepok S, Quak E, Happel M, Gaber R, Ziegler A, Schock S, Oertel WH, Sommer N, Hemmer B.
Clinical Neuroimmunology Group, Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8 and. Institute of Medical Biometry and Epidemiology, Philipps University, Bunsenstrasse 3, 35033 Marburg, Germany.
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.