Cross-regulation between distinct natural killer T cell subsets influences immune response to self and foreign antigens.
Natural killer T (NKT) cells generally recognize lipid-antigens presented in the context of the MHC class I-like molecule CD1d. CD1d-restricted NKT cells consist of two broad subsets: Type I, which express an invariant T cell receptor (TCR) and type II, which utilize diverse TCR gene segments. A major type II NKT subset has been shown to recognize a self-glycolipid, sulfatide. Both subsets play important roles in autoimmune diseases, tumor surveillance, and infectious diseases. While type I NKT cells protect from tumor growth by enhancing tumor surveillance, type II NKT cells may suppress anti-tumor immune responses. In a murine autoimmune hepatitis model, type I NKT cells contribute to pathogenesis, whereas activation of sulfatide-reactive type II NKT cells protects from disease. Sulfatide-mediated activation of type II NKT cells results in modification of dendritic cells and induction of anergy in type I NKT cells. Elucidation of this novel pathway of cross-regulation among NKT cell subsets will provide tools for intervention in autoimmune diseases and for designing strategies for effective anti-tumor immunity.
Arrenberg
Philomena
P
Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, San Diego, California, USA.
Halder
Ramesh
R
Kumar
Vipin
V
D000818:Animals; D000941:Antigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000941:Antigens