Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.
The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D018390:Gene Targeting; D006706:Homeostasis; D018796:Immunoconjugates; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007136:Immunoglobulins; D019014:fas Receptor; D003208:Concanavalin A; D000069594:Abatacept