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 αβ and τδ TCR. The level of CD28 on mature CD4⁺ and CD8⁺ αβ 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.