Cerebrospinal fluid T cells from multiple sclerosis patients recognize autologous Epstein-Barr virus-transformed B cells
The association between multiple sclerosis and Epstein-Barr virus infection could involve Epstein-Barr virus-specific T cells, provided that these T cells get access to the intrathecal compartment. We report that CD4+ T cells from the cerebrospinal fluid of six out of six multiple sclerosis patients, and four out of six patients with other neurological diseases, recognized autologous B cells transformed with Epstein-Barr virus. The cerebrospinal fluid T-cell responses were predominantly HLA-DR restricted. These T cells did not recognize B cells activated through stimulation of CD40 or the inducible autoantigen αB crystalline. These findings support that the immunological response to Epstein-Barr virus could contribute to the pathogenesis of multiple sclerosis.
Keywordscerebrospinal fluid Epstein-Barr virus multiple sclerosis T cells
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- Casetta I, Granieri E (2000). Clinical infections and multiple sclerosis: contribution from analytical epidemiology. J NeuroVirol 6 (Suppl 2): 147–151.Google Scholar
- Kurtzke JF (2000). Multiple sclerosis in time and spacegeographic clues to cause. J NeuroVirol 6 (Suppl 2): 134–140.Google Scholar
- Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P, Sondergaard L, Svejgaard A, Wucherpfennig K, Stuart DI, Bell JI, Jones EY, Fugger L (2002). A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 3: 940–943.PubMedCrossRefGoogle Scholar
- Molberg O, Mcadam SN, Korner R, Quarsten H, Kristiansen C, Madsen L, Fugger L, Scott H, Noren O, Roepstorff P, Lundin KE, Sjostrom H, Sollid LM (1998). Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 4: 713–717.PubMedCrossRefGoogle Scholar
- Schultze JL, Michalak S, Seamon MJ, Dranoff G, Jung K, Daley J, Delgado JC, Gribben JG, Nadler LM (1997). CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy. J Clin Invest 100: 2757–2765.PubMedCrossRefGoogle Scholar
- Weissert R, de Graaf KL, Storch MK, Barth S, Linington C, Lassmann H, Olsson T (2001). MHC class II-regulated central nervous system autoaggression and T cell responses in peripheral lymphoid tissues are dissociated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J Immunol 166: 7588–7599.PubMedGoogle Scholar