Compromised kidney graft rejection response in vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus

Background. In nonprimates, organ allografts are often not rejected after w ithdrawal of immunosuppression. In this study, we examined whether such a p henomenon also occurs in primates. Methods. Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro. Results. The majority (80-100%) of the grafts survived for at least additio nal 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymph ocyte reaction and interleukin-2 production in the mixed lymphocyte reactio n between the recipients and their donors or between the recipients and a t hird party had no discernable patterns, and thus did not reflect the in viv o status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-deriv ed skin grafts had pathological findings of chronic rejection. Conclusions. The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejec tion is specific and is not due to a permanent alteration of the immune sys tem by the initial drug treatment. The allografts are not inert but have lo w levels of interaction with the recipient immune system.