Until recently, it was thought that signal transduction through CD28 a
nd the related molecule CTLA4 prevented the induction of anergy in T c
ells activated through the TCR. This hypothesis has been suggested as
an explanation for how soluble forms of CTLA4, which bind the CD28/CTL
A4 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, CTL
A4-mediated signal transduction has been reported to induce cell death
in previously activated T cells. These data suggest that B7-1/B7-2 si
gnaling not only controls cell proliferation and T-helper cell subset
selection, but also T-cell survival.