Cyclophosphamide-induced tolerance in fully allogeneic heart transplantation in mice

We have established a long-lasting heart allograft tolerance in H-2-incompatible combinations by intravenous injection of 10(8) allogeneic spleen cells followed by the administration of 200 mg/kg of cyclophosphamide (CP). When C57BL/10 mice (B10, H-2b) were primed iv with 1 x 10(8) viable spleen cells from naive BALB/c mice (H-2d) and treated ip with 200 mg/kg CP 2 days later, BALB/c heart allografts were lasting in the recipients for as long as 8 weeks. On the other hand, B10 mice receiving either allogeneic spleen cells or CP rejected the heart allograft within 10 days after transplantation. A direct approach assessing the donor-reactive T cells for frequency and reactivity showed that the donor-reactive T cells were partially deleted and the rest were rendered unresponsive. CP-induced tolerance may be applied for the induction of antigen-specific tolerance to allogeneic heart transplantation.