Tolerance to allogeneic and to xenogeneic heart grafts provided by thymectomy of adult mice combined with donor cell and cyclophosphamide inoculation.

A new method of induction of tolerance to allogeneic and to xenogeneic cells is presented. It includes thymectomy of adult mice followed 1 month later by the injection of 1 X 10(8) spleen cells i.v. and i.p. administration of 200 mg of cyclophosphamide per kg 1 day after cells. This method induced prolonged survival of heterotopically transplanted neonatal C57BL/6 murine heart grafts (more than 8 months) and of August rat heart grafts (more than 2 months) in CBA mice. Tolerance to allo- or xenoantigens was formed at the cell level. Experimental animals did not produce allo- or xenohemagglutinins after graft implantation. Spleen cells of mice with surviving C57BL/6 heart grafts did not respond to C57BL/6 cells in mixed lymphocyte culture (MLC) reaction. Lymphoid cell chimerism was not observed in animals tolerant to alloantigens.