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 isle t transplant recipients are disappointingly low, and the relative cont ribution of the rejection response compared,vith the loss of islet fun ction is still unclear, We have compared the mixed lymphocyte islet co culture (MLIC) with the mixed lymphocyte acinar cell coculture (MLAC) and the mixed lymphocyte response (MLR) as in vitro models of allograf t rejection to MHC and tissue-specific antigens expressed by human isl ets and acinar cells. The reduced number of MHC class II antigen-posit ive cells in islets and acinar tissue compared to those in the stimula tor lymphocyte population of the MLR, correlated with a reduced prolif erative response in the MLIC and MLAC, Enhancement of MHC class II ant igen expression by islets using TNF alpha and IFN gamma did not increa se their stimulatory capacity in the islet cocultures, which may have been due to a corresponding absence of B7 expression. The lack of T ce ll 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 prolif eration. In conclusion, we suggest that a rejection response to islets and acinar tissue is possible due to the accompanying MHC class II-po sitive cells and that, in this model, islet and acinar-specific antige ns 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 unlikel y that this is the sole explanation, and other factors should be consi dered. (C) 1998 Elsevier Science Inc.