J Exp Med 2001 Dec 17;194(12):1789-1799
Jahng AW, Maricic I, Pedersen B, Burdin N, Naidenko O, Kronenberg M, Koezuka Y, Kumar V.
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121. Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121. Pharmaceutical Research Laboratory, Kirin Brewery Company Limited, Takasaki-shi, Gunma 37012, Japan.
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)-gamma 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 alpha-galactosylceramide (alpha-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-gamma.
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 alpha-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
PMID: 11748280 [PubMed - as supplied
PMID: 11748280 [PubMed - as supplied by publisher]