ANTITRANSFERRIN RECEPTOR MONOCLONAL-ANTIBODY - A NOVEL IMMUNOSUPPRESSANT

Background. Transferrin receptor is a widely distributed cell surface receptor present on most proliferating and highly specialized quiescen t cells. Expression of transferrin receptor on the surface of immune c ells is up-regulated during T-cell activation after the interaction of the antigen-MHC with the T cell receptor. The role of transferrin rec eptor in T-cell activation has not been well-established. Since transf errin receptor is physically associated with the CD3 zeta-chain, block ade of transferrin receptor has the potential to interfere with the T- cell signals important in transplant rejection. Methods. Anti-transfer rin receptor monoclonal antibody (mAb) was administered in vivo and in vitro to determine whether this agent was effective in prolonging all ograft survival and altering cell-mediated immunity, Results. Using do nor C57BL/6J (H2(b)) hearts transplanted to CBA/J (H2(k)) recipients, anti-transferrin receptor mAb at the time of transplantation prolonged cardiac allograft mean survival time to 25.7 +/- 0.9 days compared wi th untreated (13.3 +/- 0.6 days, P < 0.05) or isotype-matched (10.7 +/ - 0.4 days, P < 0.05) controls. Anti-transferrin receptor mAb administ ered in vivo failed to suppress the subsequent allogeneic responses, H owever, when added to culture, anti-transferrin receptor mAb suppresse d the allogeneic cytotoxic T lymphocyte response by 79-100% but not th e mixed lymphocyte response, Conclusions. These studies are the first to suggest that transferrin receptor is a potential therapeutic target for clinical transplantation. Future studies will determine the most efficacious dose and time for maximal immunosuppression and the mechan isms responsible for the immunosuppression exhibited by antitransferri n receptor mAb.