[Costimulatory molecules in autoimmunity: role of CD28/CTLA4-CD80/CD86].
Optimal T cell activation requires at least two signals. One is provided by the interaction between antigen-specific T cell receptor and antigen-MHC complexes. The other is provided by costimulatory signals. One best characterized costimulation is mediated by CD28/CTLA4-CD80/CD86 (CD28/B7). In the past decade, costimulatory signal mediated by CD28 has been shown to be critical to augment T cell proliferative response and effector function such as cytokine production. Recent intensive analysis of the CD28/B7 pathway have revealed unexpected means in which this pathway may be involved in the maintenance and breakdown of self-tolerance. In vivo studies using antagonists or transgenes of this pathway reveals that inappropriate expression of CD80, ligand for CD28/CTLA4, could induce autoimmunity and blockade of CD28/B7 pathway could ameliolate several autoimmune disease models. Furthermore, CD80 and CD86 plays differential roles for the development of autoimmune disease since helper T cell development is differentially affected by the blockade of either. CD80 or CD86 in certain conditions. More recent studies demonstrated the crucial role of CTLA4 in negatively regulating T cell activation and autoreactivity. Taken together, this pathway play pivotal roles for autoimmunity, and manipulation of this pathway raises the possibility for controlling autoimmune diseases.
Nakajima
A
A
Department of Joint Disease and Rheumatism, Nippon Medical School.
Azuma
M
M
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology; D060908:CTLA-4 Antigen; D006801:Humans; D018796:Immunoconjugates; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept