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From the Multiple Sclerosis Research and Neuroimmunology Laboratory (Drs. Kozovska, Hong, Zang, Rivera, Killian, and Zhang, and S. Li), Department of Neurology and Baylor-Methodist International Multiple Sclerosis Center; the Department of Microbiology and Immunology (Dr. Zhang), Baylor College of Medicine; and the Neurology Research Laboratory (Drs. Kozovska, Hong, Zang, and Zhang, and S. Li), Veterans Affairs Medical Center, Houston, TX.
Address correspondence and reprint requests to Dr. Jingwu Zhang, Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, NB302, Houston, TX 77030.
OBJECTIVE: To define the in vitro effects of interferon beta 1a (IFN-ß1a) on myelin basic protein (MBP)-reactive T cells and to determine its regulatory mechanism on cytokine networks in patients with MS.
METHODS: The proliferation and cytokine production of MBP-reactive T-cell clones were measured in thymidine uptake assays and ELISA respectively. The precursor frequency of MBP-reactive T cells was estimated in a microwell culture system.
RESULTS: IFN-ß inhibited the proliferation of established MBP-reactive T-cell clones, which correlated with enhanced production of anti-inflammatory interleukin (IL)-4 and IL-10, and a decrease in tumor necrosis factor alpha (TNF-
) and IFN-
. When examined with peripheral blood mononuclear cells (PBMCs), IFN-ß was found to reduce the in vitro T-cell responses to MBP, as indicated by the significantly decreased frequency of MBP-reactive T cells. The decreased frequency of MBP-reactive T cells corresponded to an augmented production of IL-4 and IL-10. Although the level of TNF- and IFN- was generally unaltered or decreased, IFN-ß appeared to enhance the production of IFN- in PBMCs derived from some individuals with MS.
CONCLUSION: Interferon beta 1a (IFN-ß) suppresses myelin basic protein (MBP)-reactive T cells and induces immune deviation toward the production of T-helper 2 cytokines, which may contribute to its therapeutic benefit in MS. The study also suggests some heterogeneity in MBP-reactive T-cell responses to IFN-ß in different individuals with MS.
Key words: Interferon beta—Multiple sclerosis—Immunology.
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