Modulation of MHC class I antigen decreases pancreatic islet immunogenicity

Pretreatment regimens directed at reducing the immunogenicity of pancreatic islets have emphasized the elimination or alteration of the major histocompatibility complex (MHC) class II-positive dendritic cells within the islet. Unfortunately, the efficacy of such pretreatment regimens has been extremely variable and the relative contribution of the dendritic cells to the overall immunogenicity of pancreatic islets has remained ambiguous. Recent evidence has suggested that the MHC class I antigen present on the endocrine cells within the islets may play an important role in the alloimmune response. This study utilized the in vitro mixed lymphocyte-islet co-culture system to determine if pretreatment of whole islets with an anti-MHC class I monoclonal antibody specific to the donor strain would block the generation of cytotoxic T lymphocytes (CTL) in the in vitro mixed lymphocyte-islet coculture. Pretreatment of B10.BR (H-2k) and DBA/2J (H-2d) islets with an allospecific anti-MHC class I monoclonal antibody blocked the generation of allospecific CTL when the pretreated islets were placed into coculture with C57Bl/6 (H-2b) splenocytes. If such a pretreatment regimen is similarly effective in vivo, it could potentially be used as an antirejection strategy in pancreatic islet allotransplantation.