Journal of NeuroVirology

, Volume 10, Issue 1, pp 52–56

Cerebrospinal fluid T cells from multiple sclerosis patients recognize autologous Epstein-Barr virus-transformed B cells

Short Communication

Abstract

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.

Keywords

cerebrospinal fluid Epstein-Barr virus multiple sclerosis T cells 

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References

  1. Ascherio A, Munch M (2000). Epstein-Barr virus and multiple sclerosis. Epidemiology 11: 220–224.PubMedCrossRefGoogle Scholar
  2. Boylston AW, Anderson RL (1979). Lymphoblastoid cell lines are polyclonal activators of human T lymphocytes. Scand J Immunol 9: 151–158.PubMedCrossRefGoogle Scholar
  3. Bray PF, Luka J, Culp KW, Schlight JP (1992). Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF, and two pentapeptide sequence identities between EBNA and myelin basic protein. Neurology 42: 1798–1804.PubMedGoogle Scholar
  4. Casetta I, Granieri E (2000). Clinical infections and multiple sclerosis: contribution from analytical epidemiology. J NeuroVirol 6 (Suppl 2): 147–151.Google Scholar
  5. Cepok S, Jacobsen M, Schock S, Omer B, Jaekel S, Boddeker I, Oertel WH, Sommer N, Hemmer B (2001). Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis. Brain 124: 2169–2176.PubMedCrossRefGoogle Scholar
  6. Ebers GC, Sadovnick AD, Risch NJ (1995). A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 377: 150–151.PubMedCrossRefGoogle Scholar
  7. Hickey WF, Hsu BL, Kimura H (1991). T-lymphocyte entry into the central nervous system. J Neurosci Res 28: 254–260.PubMedCrossRefGoogle Scholar
  8. Holmøy T, Vandvik B, Vartdal F (2003). T cells from multiple sclerosis patients recognize immunoglobulin G from the cerebrospinal fluid. Multiple Sclerosis 9: 228–234.PubMedCrossRefGoogle Scholar
  9. Ishigami T, White CA, Pender MP (1998). Soluble antigen therapy induces apoptosis of autoreactive T cells preferentially in the target organ rather than in the peripheral lymphoid organs. Eur J Immunol 28: 1626–1635.PubMedCrossRefGoogle Scholar
  10. Kurtzke JF (2000). Multiple sclerosis in time and spacegeographic clues to cause. J NeuroVirol 6 (Suppl 2): 134–140.Google Scholar
  11. 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
  12. Leen A, Meij P, Redchenko I, Middeldorp J, Bloemena E, Rickinson A, Blake N (2001). Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol 75: 8649–8659.PubMedCrossRefGoogle Scholar
  13. Levin IL, Kassandra LM, Rubertone MV, Peck CA, Lennette ET, Spiegelman DS, Ascherio A (2003). Multiple sclerosis and Epstein-Barr virus. JAMA 289: 1533–1586.PubMedCrossRefGoogle Scholar
  14. 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
  15. Munch M, Hvas J, Christensen T, Moller-Larsen A, Haahr S (1998). A single subtype of Epstein-Barr virus in members of multiple sclerosis clusters. Acta Neurol Scand 98: 395–399.PubMedCrossRefGoogle Scholar
  16. Munz C, Bickham KL, Subklewe M, Tsang ML, Chahroudi A, Kurilla MG, Zhang D, O’Donnell M, Steinman RM (2000). Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med 191: 1649–1660.PubMedCrossRefGoogle Scholar
  17. Rønningen KS, Spurkland A, Iwe T, Sollid LM, Vartdal F, Thorsby E (1991). Novel HLA-DR2 and -DR3 haplotypes among Norwegian Caucasians. Tissue Antigens 37: 65–167.CrossRefGoogle Scholar
  18. Savoldo B, Cubbage ML, Durett AG, Goss J, Huls MH, Liu Z, Teresita L, Gee AP, Ling PD, Brenner MK, Heslop HE, Rooney CM (2002). Generation of EBV-specific CD4+ cytotoxic T cells from virus naive individuals. J Immunol 168: 909–918.PubMedGoogle Scholar
  19. 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
  20. Sutkowski N, Conrad B, Thorley-Lawson DA, Huber BT (2001). Epstein-Barr virus transactivates the human endogenous retrovirus HERV-K18 that encodes a super-antigen. Immunity 15: 579–589.PubMedCrossRefGoogle Scholar
  21. van Noort JM, Bajramovic JJ, Plomp AC, van Stipdonk MJ (2000). Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis. J Neuroimmunol 105: 46–57.PubMedCrossRefGoogle Scholar
  22. van Sechel AC, Bajramovic JJ, van Stipdonk MJ, Persoon-Deen C, Geutskens SB, van Noort JM (1999). EBV-induced expression and HLA-DR-restricted presentation by human B cells of alpha B-crystallin, a candidate autoantigen in multiple sclerosis. J Immunol 162: 129–135.PubMedGoogle Scholar
  23. Waldmann TA (1986). The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science 232: 727–732.PubMedCrossRefGoogle Scholar
  24. 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
  25. Wucherpfennig KW, Strominger JL (1995). Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80: 695–705.PubMedCrossRefGoogle Scholar
  26. Zamvil S, Nelson P, Trotter J, Mitchell D, Knobler R, Fritz R, Steinman L (1985). T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317: 355–358.PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2004

Authors and Affiliations

  1. 1.Institute of ImmunologyRikshospitalet University HospitalOsloNorway

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