The potential contribution of rejection to survival of transplanted human islets

Clinical islet transplantation is potentially the treatment of choice for people with type I diabetes. Rates of insulin independence in islet transplant recipients are disappointingly low, and the relative contribution of the rejection response compared,vith the loss of islet function is still unclear, We have compared the mixed lymphocyte islet coculture (MLIC) with the mixed lymphocyte acinar cell coculture (MLAC) and the mixed lymphocyte response (MLR) as in vitro models of allograft rejection to MHC and tissue-specific antigens expressed by human islets and acinar cells. The reduced number of MHC class II antigen-positive cells in islets and acinar tissue compared to those in the stimulator lymphocyte population of the MLR, correlated with a reduced proliferative response in the MLIC and MLAC, Enhancement of MHC class II antigen expression by islets using TNF alpha and IFN gamma did not increase their stimulatory capacity in the islet cocultures, which may have been due to a corresponding absence of B7 expression. The lack of T cell proliferation to acinar cells despite cytokine-induced enhancement of MHC class II expression and detectable B7 expression appeared to be due to the inhibitory effect of exocrine enzymes on lymphocyte proliferation. In conclusion, we suggest that a rejection response to islets and acinar tissue is possible due to the accompanying MHC class II-positive cells and that, in this model, islet and acinar-specific antigens do not significantly contribute to that response. Acinar cells may have the potential to stimulate lymphocytes directly, but this was not evident by proliferation in the MLAC, Rejection appears to contribute to the low survival rate of human islet allografts, but it is unlikely that this is the sole explanation, and other factors should be considered. (C) 1998 Elsevier Science Inc.