Natural killer T cells as targets for immunotherapy of autoimmune diseases.
CD1d-restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during an immune response. The identification of alpha-galactosylceramide (alpha-GalCer), a marine sponge-derived glycosphingolipid, as a potent stimulator of NKT cells led many laboratories to investigate the effects of NKT cell activation on the regulation of immune responses. These studies revealed that alpha-GalCer induces rapid and robust cytokine production by NKT cells, secondary activation of a variety of innate and adaptive immune cells, and modulation of Th cell responses. Further, alpha-GalCer influences disease progression in a variety of experimental models of autoimmunity and inflammation in mice, including models for type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and atherosclerosis. While these studies have raised significant enthusiasm for manipulation of NKT cells as a means of preventing autoimmunity in the clinical setting, there are significant concerns regarding the safety of repeated alpha-GalCer injections in human subjects.
Van Kaer
Luc
L
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. luc.van.kaer@vanderbilt.edu
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide