PROLONGATION OF IN-VIVO MOUSE ISLET ALLOGRAFT SURVIVAL BY MODULATION OF MHC CLASS-I ANTIGEN

Major histocompatibility complex class I-deficient islets from beta-2 microglobulin-deficient mice have been shown to have prolonged in vivo islet allograft survival. Additionally in vitro studies using the mix ed lymphocyte islet coculture system have demonstrated a reduction in cytotoxic T lymphocyte activity against alloislets that have been pret reated with an antibody directed against MHC class I antigen. The clin ical applicability of these findings are examined in this study, which evaluates the ability of MHC class I blocking antibody to prevent the in vivo destruction of alloislets. Recipients of allogeneic islet tra nsplants treated with phosphate-buffered saline or control F(ab'), fra gments rejected the transplanted alloislets in median times of 11.5 da ys and 11 days, respectively. Recipient mice treated with a monoclonal antibody or F(ab'), fragments specific to the donor MHC class I antig en had significant prolongation in allograft survival (median allograf t survival for both groups was 21 days) when compared with mice treate d with PBS or control F(ab'), fragment. These results demonstrate that treating recipients of alloislets with donor-specific MHC class I mon oclonal antibody or the respective F(ab'), fragments prolongs islet al lograft survival. This confirms the importance of MHC class I antigen in the rejection of pancreatic islet allografts and suggests that bloc king different domains on the MHC class I molecule could be used thera peutically in the protection of allografts from the immune system.