Intercellular adhesion molecule 1 is critical for activation of CD28-deficient T cells

Presentation of Ag to T lymphocytes in the absence of the requisite costimu latory signals leads to an Ag-specific unresponsiveness termed anergy, wher eas Ag presentation in conjunction with costimulation leads to clonal expan sion, B7/CD28 signaling has been shown to provide this critical costimulato ry signal and blockade of this pathway may inhibit in vitro and in vivo imm une responses. Although T cells from CD28-deficient mice are lacking in a v ariety of responses, they nonetheless are capable of various primary and se condary responses without the induction of anergy expected in the absence o f costimulation, This suggests that there may be alternative costimulatory pathways that can replace CD28 signaling under certain circumstances. In th is paper, we show that ICAM-1becomes a dominant costimulatory molecule for CD28-deficient T cells. ICAM-1 costimulates anti-CD3-mediated T cell prolif eration and IL-2 secretion in CD28-deficient murine T cells. Furthermore, s plenocytes from ICAM-1-deficient mice could not activate CD28-deficient T c ells and splenocytes lacking both ICAM and CD28 fail to proliferate in resp onse to anti-CD3-induced T cell signals. This confirms that not only can IC AM-1 act as a CD28-independent costimulator, but it is the dominant, requis ite costimulatory molecule for the activation of T cells in the absence of B7/CD28 costimulation.