Intestinal allograft survival in the rat following pretreatment with donor-specific UV-B-irradiated leukocytes and peritransplant immunosuppression with cyclosporine

Abstract

Abstract. Previous studies from our laboratory showed that pretreatment with ultraviolet-B-irradiated donor leukocytes (UV-B DL) combined with brief peritransplant cyclosporine (CyA) resulted in indefinite survival of Wistar/Furth rat cardiac allografts in Lewis recipients, This study was designed to examine the effect of pre-transplant UV-B DL with or without peritransplant CyA on orthotopic intestinal allografts in the same rat strain combination. The results showed that while low-dose CyA treatment alone (10 mg/kg i.m. on days 0, +1, and + 2) had no effect on intestinal allograft rejection, 20 mg/kg (on days 0, + 1, and + 2) CyA significantly (P< 0.001) prolonged graft survival, with 33% of the hosts surviving indefinitely. The highest dose of CyA (30 mg on days 0, + 1, and + 2) abrogated rejection, but most transplant recipients succumbed to infection and functional ileus due to a toxic side effect of CyA. Pretreatment with UV-B DL on days-14 and-7 alone did not prolong intestinal allograft survival. Combination of a subtherapeutic CyA dose (20 or 10 mg/kg) given on days 0, + 1, and + 2 with pretransplant UV-B DL on days-14 and-7 did not alter the survival of intestinal allografts compared to treatment with CyA alone. This suggests that pretreatment with UV-B DL with or without peritransplant administration of CyA has no effect on intestinal allograft survival, in contrast to the effect of such combined treatm̂ent on cardiac allograft survival, where indefinite graft survival is observed. This difference in the effect of pretransplant UV-B DL on intestinal and cardiac allograft survival is most likely due to organ-specific immunogenicity, particularly to the relative density of class I and II histocompatibility antigens present in heart or intestine.