Background: The monoclonal antirat CD4 antibody RIB 5/2 has been shown to modulate the CD4 glycoprotein without eliminating the affected T cells. We have shown that the administration of multiple doses of RIB 5/2 during the peritransplantation period prevents the rejection of rat kidney allografts.
Methods: We compared the efficacy of a single intraperitoneal dose of 20 mg/kg RIB 5/2 plus donor antigen (25 x 10(6) spleen cells [SCs]) given by either an intrathymic or an intravenous route with the depleting anti-CD4 monoclonal antibody (mAb) OX-38 plus antigen 21 days before a major histocompatibility complex (MHC)-mismatched Lewis (RT1l) to Buffalo (RT1b) rat cardiac or renal allograft. By delaying the transplantation for 21 days, recovery from the nonspecific effects of the antibody treatment allowed the demonstration of donor antigen-specific tolerance.
Results: OX-38 mAb given with intrathymic SCs induced tolerance to heart but not kidney grafts, whereas OX-38 given with intravenous SCs failed to prolong survival of either heart or renal allografts. In contrast, RIB 5/2 mAb administration, when combined with alloantigen given by either intravenous or intrathymic routes, induced tolerance to heart allografts, whereas only alloantigen given by the intravenous route with RIB 5/2 resulted in tolerance to renal grafts.
Conclusions: Concomitant administration of intravenous donor alloantigen and the modulation of CD4+ recipIent cells by nondepleting RIB 5/2, rather than elimination of these CD4+ cells with depleting mAb OX-38, is a more potent method for the induction of allograft tolerance.