International Immunology, Vol. 12, No. 12, 1641-1650,
December 2000
© 2000 Japanese Society for Immunology
Aberrant T cell responses to myelin antigens during clinical exacerbation in patients with multiple sclerosis
1 Multiple Sclerosis Research Laboratory, Baylor-Methodist Multiple Sclerosis Center and Department of Neurology
2 Neurology Research Laboratory, Veterans Affairs Medical Center, and
3 Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
4 Tissue-Typing Laboratory, Academic Hospital, University of Limburg, 6202 AZ Maastricht, The Netherlands
Correspondence to: J. Zhang, Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, NB302, Houston, TX 77030, USA
Multiple sclerosis (MS) is a demyelinating disease of presumed T cell autoimmunity against self myelin. We hypothesized that if myelin-reactive T cells are associated with the disease processes, they may undergo activation and expansion during acute exacerbation. In this study, we examined the precursor frequency, epitope recognition and cytokine profile of myelin-reactive T cells in 14 relapsing/remitting MS patients during exacerbation and remission. The study revealed that T cells recognizing the immunodominant peptides of candidate myelin antigens, including myelin basic protein (MBP), proteolipid protein and myelin oligodendrocyte glycoprotein, occurred at increased precursor frequency during acute exacerbation. The T cell responses to MBP focused on the immunodominant regions (residues 83–99 and 151–170) during exacerbation and shifted toward other epitopes of MBP at the time of remission. Furthermore, there was a marked increase in the production of Th1 cytokines among T cell lines obtained during exacerbation compared to those obtained during remission. The study demonstrated that myelin-reactive T cells underwent selective activation and expansion during acute MS exacerbation. In contrast, myelin-reactive T cells found during remission in the same patients generally resembled those identified in healthy controls with some discrepancies. The findings suggest potential association of aberrant myelin-reactive T cell responses with acute exacerbation in MS, which may reflect transient activation of myelin-reactive T cell populations of pathogenic potential.
Keywords: myelin, multiple sclerosis, T cells
Transmitting editor: L. Steinman
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