CD28 AND APOPTOSIS

Until recently, it was thought that signal transduction through CD28 and the related molecule CTLA4 prevented the induction of anergy in T cells activated through the TCR. This hypothesis has been suggested as an explanation for how soluble forms of CTLA4, which bind the CD28/CTLA4 ligands B7-1 and B7-2, can prevent graft rejection. Recent reports suggest that another function of CD28 costimulation is the regulation of T-cell survival. CD28 not only enhances IL-2 production, which can act as an extrinsic regulator of cell survival, but also augments the expression of the intrinsic survival factor Bcl-x(L). In contrast, CTLA4-mediated signal transduction has been reported to induce cell death in previously activated T cells. These data suggest that B7-1/B7-2 signaling not only controls cell proliferation and T-helper cell subset selection, but also T-cell survival.