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¹ Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
² Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
³ Pharmaceutical Research Laboratory, Kirin Brewery Company Limited, Takasaki-shi, Gunma 37012, Japan

Address correspondence to Dr. Vipin Kumar, Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: 858-678-4564; Fax: 858-558-3525; E-mail: vipink{at}liai.org

Natural killer (NK) T cells recognize lipid antigens in the context of the major histocompatibility complex (MHC) class 1–like molecule CD1 and rapidly secrete large amounts of the cytokines interferon (IFN)- and interleukin (IL)-4 upon T cell receptor (TCR) engagement. We have asked whether NK T cell activation influences adaptive T cell responses to myelin antigens and their ability to cause experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. While simultaneous activation of NK T cells with the glycolipid -galactosylceramide (-GalCer) and myelin-reactive T cells potentiates EAE in B10.PL mice, prior activation of NK T cells protects against disease. Exacerbation of EAE is mediated by an enhanced T helper type 1 (Th1) response to myelin basic protein and is lost in mice deficient in IFN-. Protection is mediated by immune deviation of the anti-myelin basic protein (MBP) response and is dependent upon the secretion of IL-4. The modulatory effect of -GalCer requires the CD1d antigen presentation pathway and is dependent upon the nature of the NK T cell response in B10.PL or C57BL/6 mice. Because CD1 molecules are nonpolymorphic and remarkably conserved among different species, modulation of NK T cell activation represents a target for intervention in T cell–mediated autoimmune diseases.

Key Words: NK T cells • CD1d • experimental autoimmune encephalomyelitis • immunotherapy • -galactosylceramide

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