THE ROLE OF DONOR AND RECIPIENT B7-1 (CD80) IN ALLOGRAFT-REJECTION

Blockade of CD28-mediated T cell costimulatory signals produces effect ive immunosuppression of a variety of T cell-dependent in vivo immune responses, including autoimmune disorders and transplant rejection, Th e soluble fusion protein CTLA4Ig, which competitively blocks CD28 liga nds B7-1 and B7-2, can prevent allograft and xenograft rejection and i n some circumstances induce transplantation tolerance, To determine th e relative roles of B7-1 and B7-2 in graft rejection, we have performe d islet and cardiac allografts with normal and B7-1(-/-) mice in conju nction with selective blocking reagents, We found that the absence of B7-1 on donor or recipient tissues leads to a slight prolongation of i slet allograft survival, but has minimal or no effect on cardiac allog raft survival. Allograft function is further prolonged in the islet mo del when both donor and recipient lack B7-1, although cardiac allograf t survival is not prolonged, In the cardiac model, treatment with CTLA 4Ig induces long term survival in B7-1(-/-) recipients regardless of d onor status, In contrast, anti-B7-2 mAb leads to indefinite allograft survival only when the recipient and donor both lack B7-1, indicating that even in the absence of available B7-2, B7-1 molecules on the dono r or recipient cells alone are sufficient to induce graft rejection. T hese data also indicate that B7-1 and B7-2 are the only CD28 ligands r elevant to cardiac allograft rejection in mice.