Durable donor-specific T and B cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin - Absence of chronic allograft nephropathy

Tolerance induction can prevent acute kidney allograft rejection without ch ronic immunosuppression. It is uncertain whether specific tolerance can pre vent chronic allograft nephropathy (CAN), which involves both nonimmune and immune injury. This report provides evidence that immunologically tolerant macaques, induced with immunotoxin and deoxyspergualin, developed neither acute rejection nor CAN. Long survivors, bearing MHC-mismatched grafts with out chronic immunosuppression for 0.8 to 3.4 years, exhibited general immun e competence with donor-specific T and B cell tolerance and no functional o r histological evidence of CAN. Stringent criteria for tolerance were satis fied by specific prolongation of donor skin grafts with rapid rejection of third-party skin, followed by indefinite acceptance of a second donor kidne y graft and establishment of microchimerism. Primate tolerance with documen ted absence of CAN may give impetus to the clinical application of toleranc e.