Prior pancreatic islet transplantation mitigated the subsequent skin graft rejection against HY disparity in C57BL/6 with pre-existing immunological memory (126.15)

Abstract

Abstract Several successful immunomodulatory strategies in specific pathogen-free rodents have failed in outbred larger animals by pre-existing memories. In our previous report, we showed that the islet transplantation across the minor histocompatibility of HY (male antigen) could induce immunological tolerance to male antigen in female C57BL/6 mice. In this study, we tested whether islet-transplantation-induced immunological tolerance could be achieved against the barrier of pre-existing immunological memory. Splenocytes isolated from male C57BL/6 were injected into syngeneic female mouse intraperitoneally. The induction of memory was confirmed by accelerated male skin rejection from 27 days (naïve control mouse) to 19 days. The islets isolated from male C57BL/6 mice were transplanted into renal subcapsule of the sensitized mice. 37.5% of sensitized recipients rejected male islets, whereas 100% of naïve recipients accepted the grafts. Remaining 62.5% of sensitized recipients that accepted male islets did not accept subsequent male skin graft. Although male skin graft failed to be accepted in the male islet-accepted recipients, the intensity of inflammatory response was significantly lower than that shown in presensitized mice without male islet graft. In conclusion, the islet-transplantation-induced immunological tolerance could not circumvent the barrier of immunological memory, however, it could mitigate the intensity of inflammatory rejection process.