Xenogeneic islet re-transplantation in mice triggers an accelerated, species-specific rejection

Xenogeneic islets could provide an unlimited source of tissue for the treat ment of diabetes, and could in theory be transplanted repeatedly in a recip ient. However, little is known on the consequences of islet re-transplantat ion in a recipient who has rejected a first graft. In this study, we invest igated the functional consequence of xeno islet re-transplantation in mice sensitized with islets from different species. Sprague-Dawley (SD)-rat isle ts transplanted in sensitized C57/B16 mice that rejected either SD- or Lewi s-rat islets underwent accelerated rejection. However, accelerated rejectio n was not found in mice sensitized with pig or human islets, suggesting tha t accelerated rejection was species specific. Immunohistochemistry showed i ncreased binding of antibodies and accelerated leucocyte infiltration on re -grafted islets in sensitized mice. In situ apoptosis detection indicated t hat islet cell apoptosis was correlated with the time of leucocyte infiltra tion, but not with the time of antibody binding. In vitro experiments with cultured islet cells showed that although antibody binding was increased af ter incubation with sensitized mouse serum, islet cell cytotoxicity was not increased, suggesting that humoral immunity did not play a direct role in islet destruction. These results indicate that there is a cell-mediated, sp ecies-specific accelerated rejection after re-transplantation of xenogeneic islets.