Intrathymmic donor antigen in baboon kidney allotransplantation

Rats may be rendered tolerant to allografts by a single intrathymic injection (IT) of donor cells given 0-21 days before transplantation with or without immunosuppression. This prompted us to use these procedures in subhuman primates given renal allografts after lymphoablation. Timing of donor antigen was adapted to circumstances of clinical cadaver transplantation. Median survival (MS) of recipient baboons given IT donor spleen cells after immunosuppression with anti-thymocye globulin (ATG; MS=7d) or in combination with cyclosporin A and dexamethasone (MS=13d) was disappointing when compared with untreated controls (MS=11d). Immmunosuppression with total lymphoid irradiation (TLI) + ATG and IT donor spleen cells increased MS to 22d and 41d respectively. IT donor glomeruli in combination with TLI increased MS to 242d, a value previously obtained with TLI alone. Some animals given IT spleen a week before transplant showed evidence of sensitization. Immunosuppression reduced interleukin-2 synthesis in recipient lymphocytes and MLC suppressive serum factors occurred in 4 long-surviving baboons which had received TLI. Injection of donor cells into the atrophied thymus of adult baboons is difficult, and leakage of foreign cells or soluble antigen might have triggered host immunity in early rejectors. This is an important consideration in the clinical application of the approach.