Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis.
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 diseases.
Jahng
A W
AW
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Maricic
I
I
Pedersen
B
B
Burdin
N
N
Naidenko
O
O
Kronenberg
M
M
Koezuka
Y
Y
Kumar
V
V
D000818:Animals; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005699:Galactosylceramides / Q000276:immunology; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000276:immunology
D018949:Antigens, CD1; C419394:CD1b antigen; D005699:Galactosylceramides