LONG-TERM IN-VIVO EFFECTS OF RAPAMYCIN ON HUMORAL AND CELLULAR IMMUNE-RESPONSES IN THE RAT

Rapamycin (RAPA) is a strong immunosuppressant and is able to prevent allograft rejection in animal models. We have demonstrated that RAPA c ould strongly inhibit in vitro immunoglobulin (Ig) production by human lymphocytes. The present study investigated the long-term in vivo eff ect of RAPA on humoral and cellular immune responses, and the effect o f RAPA on accelerated rejection. It was shown that RAPA strongly inhib ited antigen (Ag) specific antibody (AB) production (i.e. cytotoxic Ab to donor lymphocytes and Ab to tetanus toxoid) during the period of d rug administration. The accelerated rejection of cardiac allografts in presensitized animals was alleviated by RAPA administration. These re sults suggest the potential application of RAPA in treatment of presen sitized candidates for organ transplantation. A little more than two m onths after the drug withdrawal, the rats were basically competent in Ab response to further Ag challenges. When tested 4 months after the R APA-treatment, the rats showed uncompromised cardiac allograft rejecti on, and the cellular immune response in vitro according to mixed lymph ocyte reaction (MLR) and mitogen-stimulated proliferation were not ham pered. Such results suggest that the immune system can return to norma l status without sequelae after discontinuation of RAPA.