Cyclosporine facilitates chimeric and inhibits nonchimeric tolerance afterposttransplant total lymphoid irradiation

Background. previous studies showed that Lewis rats given posttransplant to tal lymphoid irradiation, antithymocyte globulin, and a single infusion of ACI peripheral blood or bone marrow cells develop tolerance to ACI heart al lografts. Methods. To determine the effects of cyclosporine on these tolerance induct ion protocols, groups of Lewis hosts, given either ACI blood or marrow infu sions, were given a 60-day course of daily cyclosporine immediately after t he cell infusion. Results. Cyclosporine treatment was associated with uniform graft rejection in the groups given an ACI blood transfusion, and was associated with unif orm graft acceptance in the groups given an ACI bone marrow infusion, Studi es of donor-type T and B cell chimerism in the host blood showed that cyclo sporine facilitated chimerism in the hosts given ACI bone marrow cells, and stable chimerism over a 300-day observation period was predicted by detect able chimerism by day 30. None of the hosts given ACI blood cells developed chimerism. Conclusion. Cyclosporine facilitated long-term graft acceptance in a toleri zation protocol that induced mixed chimerism, but prevented long-term graft acceptance in a tolerization protocol that did not induce chimerism.