Cross‐regulation between distinct natural killer T cell subsets influences immune response to self and foreign antigens

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Abstract
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. J. Cell. Physiol. 218: 246–250, 2009.

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