Identification and distribution of the costimulatory receptor CD28 in the mouse.
T cell activation requires Ag-specific stimulation mediated by the TCR as well as an additional stimulus provided by Ag presenting cells. On human T cells, it has been shown that antibodies to the Ag CD28 can provide a potent amplification signal for cytokine production and proliferation. Here we describe the production of a mAb to the murine homologue of CD28, and the use of this antibody to examine the function and distribution of CD28 in the mouse. Anti-murine CD28 synergizes with TCR-mediated signals to greatly enhance lymphokine production and proliferation of T cells, and the CD28 signal is not blocked by cyclosporin A. In the peripheral lymphoid organs and in the blood of the mouse, all CD4+ and CD8+ T cells express CD28. In the thymus, CD28 expression is highest on immature CD3-, CD8+ and CD4+8+ cells, and on CD4-8- cells that express alpha beta and tau delta TCR. The level of CD28 on mature CD4+ and CD8+ alpha beta TCR+ thymocytes is two- to fourfold lower than on the immature cells. The potent costimulatory function of CD28 on mature T cells, together with the high level of expression on CD4+8+ thymocytes, suggest that this costimulatory receptor might play an important role in T cell development and activation.
Gross
J A
JA
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Callas
E
E
Allison
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D018106:CD28 Antigens; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000276:immunology; D007106:Immune Sera / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D007106:Immune Sera; D007376:Interleukin-2; D016572:Cyclosporine