DIFFERENTIAL IMMUNOSUPPRESSIVE ACTIVITY OF MONOCLONAL CD2 ANTIBODIES ON ALLOGRAFT-REJECTION VERSUS SPECIFIC ANTIBODY-PRODUCTION

CD2 is a co-stimulatory receptor involved in T cell activation. Here w e report on immunosuppressive effects of three mouse CD2 monoclonal an tibodies (OX34, OX54, OX55) directed against non-overlapping epitopes of the rat CD2 receptor on various modes of T cell activation in vitro and in vivo. Although non-ligand-blocking OX54 and OX55, in concert, activated T cells through CD2 in vitro, they individually suppressed t he mixed lymphocyte reaction (MLR) and significantly prolonged allogra ft survival after rat heart transplantation in vivo. Phenotype analysi s revealed that OX55 significantly down-modulated CD2 in vivo, whereas OX54 depleted T cells. Graft rejection coincided with re-expression o f CD2 and clearance of OX55 from serum, whereas T cell depletion by OX 54 outlasted the period of graft survival. The most suppressive antibo dy, OX34, down-modulated CD2 and inhibited T cell activation through t he TCR or CD2 and the MLR and prolonged median allograft survival time from 7 days in controls to 45 days in the absence of any additional t reatment. Graft survival was clearly dose dependent and correlated wit h the duration of CD2 down-modulation and the presence of circulating CD2 antibody in serum. Importantly, the specific antibody production t o a T cell-dependent antigen as demonstrated by immunization with keyh ole limpet hemocyanin in vivo remained unaffected after treatment with OX34. These results demonstrate the pivotal role of CD2 signaling in mediating allogeneic immune reactions after vascularized organ transpl antation while allowing specific humoral immune responses in vivo.