RECIPIENT CELLS EXPRESSING SINGLE-DONOR MHC LOCUS PRODUCTS CAN SUBSTITUTE FOR DONOR-SPECIFIC TRANSFUSION IN THE INDUCTION OF TRANSPLANTATION TOLERANCE WHEN PRETREATMENT IS COMBINED WITH ANTI-CD4 MONOCLONAL-ANTIBODY - EVIDENCE FOR A VITAL ROLE OF CD4(-CELLS IN THE INDUCTION OF TOLERANCE TO CLASS-I MOLECULES() T)

Syngeneic cells expressing single donor MHC locus products have been s hown to induce specific immunological hyporesponsiveness, but not tole rance, to an allograft. In this study we have attempted to potentiate the beneficial effect of pretreatment with single donor MHC locus prod ucts by the addition of anti-Cd4(2) monoclonal antibody to the pretrea tment protocol. We show that pretreatment with recipient L cells expre ssing the products of a single donor locus (K, D, or FA) can induce to lerance to a C57BL/10 (H2(b)) cardiac allograft in C3H/He (H2(k)) mice , when given in combination with the depleting anti-Cd4 monoclonal ant ibody YTA 3.1.2. Both the induction and maintenance phases of toleranc e were found to be antigen-specific. Cells expressing donor class II a ntigens, IA(b), were found to be most effective. Interestingly, donor class I molecules were also found to be capable of inducing specific u nresponsiveness in combination with anti-Cd4, provided an optimal anti genic load was delivered at the time of pretreat ment. Pretreatment wi th cells expressing donor class I and anti-Cd8 monoclonal antibody had no beneficial effect on graft survival. These data show that single d onor MHC locus products can induce immunologic tolerance to fully MHC and minor histocompatibility antigen-mismatched heart grafts when give n under the cover of anti-Cd4 mAb. They also show that Cd4(+) T cells play an important role in the induction of specific unresponsiveness t o class I alloantigen in vivo and suggest that the blockade of T cells capable of recognizing class I alloantigen presented indirectly is im portant in the induction of tolerance.