Regulation of immune responses by CD1d-restricted natural killer T cells.
Natural killer T (NKT) cells are a unique subset of T lymphocytes that share receptor structures and properties with conventional T lymphocytes and natural killer (NK) cells. NKT cells are specific for glycolipid antigens such as the marine sponge-derived agent alpha-galactosylceramide (alpha-GalCer) presented by the major histocompatibility complex (MHC) class I-like molecule CD1d. My laboratory has evaluated the function of NKT cells by generating and analyzing CD1d-deficient mice. These studies showed that CD1d expression is required for NKT cell development, but not absolutely necessary for the generation of polarized T helper (Th) cell responses. Further, we have studied the in vivo response of NKT cells to alpha-GalCer stimulation and the capacity of alpha-GalCer to modulate innate and adaptive immune responses. Our results revealed that, quickly following administration of alpha-GalCer, NKT cells expand and produce cytokines, trans-activate a variety of innate and adaptive immune cells, and promote Th2 responses that are capable of suppressing Th1-dominant autoimmunity. Our findings indicate that NKT cells play a regulatory role in the immune response and that specific activation of these cells may be exploited for therapeutic purposes.
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA. luc.van.kaer@vanderbilt.edu
Luc
L
Van Kaer
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; D015395:Histocompatibility Antigens Class I; C493154:alpha-galactosylceramide