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Brain, Vol. 125, No. 3, 538-550, March 2002
© 2002 Guarantors of Brain

Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients

Marc Jacobsen1, Sabine Cepok1, Elfriede Quak1, Michael Happel1, Rami Gaber1, Andreas Ziegler2, Sabine Schock1, Wolfgang H. Oertel1, Norbert Sommer1 and Bernhard Hemmer1

1 Clinical Neuroimmunology Group, Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8 and 2 Institute of Medical Biometry and Epidemiology, Philipps University, Bunsenstrasse 3, 35033 Marburg, Germany

Correspondence to: B. Hemmer, Clinical Neuroimmunology Group, Department of Neurology, Philipps University, Rudolf-Bultmann Strasse 8, 35033 Marburg, Germany E-mail: hemmer{at}mailer.uni-marburg.de

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 ß (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 ß- 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.


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