Regulation of immune and autoimmune responses by ICOS.
Proper T cell activation and function are regulated by the innate immune system, importantly through positive and negative costimulatory molecules in the B7 superfamily. Inducible costimulator (ICOS), the receptor for B7h (also known as B7RP-1), is expressed on T cells after T cell activation. Recently, using ICOS-deficient mice, we have examined the roles of ICOS in immune responses. ICOS is required for humoral immunity. In organ-specific autoimmune responses, however, ICOS has contrast roles in different disease models. On the one hand, ICOS-/- mice exhibited extreme sensitivity to experimental autoimmune encephalomyelitis (EAE); on the other, ICOS gene deletion led to complete resistance to collagen-induced arthritis (CIA) in mice. Our work not only illustrates the complexity of immune regulation by costimulatory molecules, but also suggests novel therapeutic strategies for various autoimmune diseases.
Department of Immunology, University of Washington, 1959 NE Pacific Street, H466 HSC, Seattle, WA 98195-7650, USA. chendong@u.washington.edu
Chen
C
Dong
Roza I
RI
Nurieva
D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D001169:Arthritis, Experimental / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006801:Humans; D007109:Immunity / Q000502:physiology*; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein