Variable allograft responses to pretreatment with donor splenocytes treated with mitomycin C in the rat

In an attempt to investigate the nonspecificity of the effect of administration of donor splenocytes treated with mitomycin C (MMC) 7 days before transplantation in inducing immunological unresponsiveness, the survival rates of liver, heart, small bowel, and skin allografts were compared in the RTl-incompatible ACI(RT1⁸) to LEW(RT1¹) rat combination. ACI donor splenocytes (3×10⁶) treated with MMC were administered i.p. or i.v. via the penile vein 7 days before transplantation. Both routes of administration prolonged the survival of hepatic allografts (>87.2±22.2 days and >78.9±28.2 days, respectively), compared with controls (10.6±0.5 days). Cardiac allograft survival in untreated controls was 6.0±0.4 days. A single i.v. injection of 3×10⁶ donor splenocytes resulted in significantly prolonged survival (10.0±4.3 days), whereas i. p. injection showed rejection at a mean of 6.0±1.2 days. A single i.p. injection of 3×10⁶ splenocytes did not increase survival of small bowel allografts (10.3±4.8 days), compared with controls (8.8±1.8 days). On the other hand, a single i.v. injection of donor splenocytes prior to transplantation significantly prolonged survival of small bowel allografts (13.4±3.5 days). No signs of graft- versus-host reaction (GVHR) were observed during these experiments. Neither a single i.p. nor a single i.v. injection of donor splenocytes resulted in prolonged survival of ACI-to-LEW skin allografts (6.3±0.8 days and 6.6±0.9 days, respectively), compared with controls (5.7±0.5 days). Interestingly, we confirmed the relative ease with which survival of hepatic allografts can be prolonged in the rat by donor antigen treatment alone, even in a strongly rejecting RTl-incompatible rat strain combination, in contrast to other organ allografts such as heart, small intestine, and skin. The discrepancy in survival of different organ allografts following pre-treatment with donor splenocytes treated with MMC may be explained by a difference in the immunogenicity of the organs transplanted or other factors.