CTLA-4: a key regulatory point in the control of autoimmune disease.
Chronic autoimmune disease in humans is the result of a failure to control autoreactive immune cells in the periphery. This control is largely achieved by inhibition of newly activated and memory cells. A number of negative immune regulatory pathways have been characterized. The cell surface coreceptor cytotoxic T-lymphocyte antigen-4 (CTLA-4) has emerged as a critical attenuator of T-cell activation and an essential component of the regulatory systems that serve to maintain peripheral tolerance. CTLA-4 expression is induced on the surface of T cells after they have received a costimulatory signal from antigen-presenting cells (APCs) via engagement of CD28 on the T-cell surface. CTLA-4 attenuates this costimulation by competing for CD28 ligands and through direct effects on APCs via the same ligands utilized by CD28. A large number of genetic association studies suggest that the CTLA-4 gene is a locus of susceptibility to autoimmune disease. However, specific functional defects in the CTLA-4 gene in patients have not been identified to date. Elucidating the role of CTLA-4 in immune tolerance has also led to a number of therapeutic applications, particularly in the treatment of malignancy and autoimmune disease.
Scalapino
Kenneth J
KJ
Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA 94121, USA.
Daikh
David I
DI
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D004198:Disease Susceptibility; D015536:Down-Regulation; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates / Q000276:immunology* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000627:therapeutic use; D008213:Lymphocyte Activation; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept