The role of CD154 in organ transplant rejection and acceptance

CD154 plays a critical role in determining the outcome of a transplanted or gan. This simple statement is amply supported by experimental evidence demo nstrating that anti-CD154 antibodies are potent inhibitors of allograft rej ection in many rigorous transplant models. Unfortunately; despite intensive investigation over the past ten years, the precise mechanisms by which ant ibodies against CD154 exert their anti-rejection effects have remained less obvious. Though originally classified with reference to B-cell function, C D154-CD40 interactions have also been shown to be important in T cell-antig en-presenting cell interactions. Accordingly; CD154 has I,een classified as a T-cell co-stimulator) molecule. However, mounting data suggest that trea tment with anti-CD154 antibodies does not simply block co-stimulatory signa ls, but rather that the antibodies appear to induce signalling in receptor- bearing T cells. Other data suggest that anti-CD154 effects may be mediated hy endothelial cells and possibly even platelets. In fact, tile current li terature suggests that CD154 can either stimulate or attenuate an immune re sponse, depending upon the model system under study. CD154 has secured a fu ndamental place in transplant biology and general immunology that will no d oubt be the source of considerable investigation and therapeutic manipulati on in the coming decade.