In human islet transplantation (ITX), the impact of donor-recipient major histocompatibility complex (MHC) matching on transplant survival is currently unknown. Utilizing defined MHC mismatches, we have investigated the outcome of ITX in naïve and presensitized congenic Lewis rats. ITX into streptozotocin diabetic Lewis rats was performed under the kidney capsule. Presensitization by skin transplantation was performed on days 1, 28, and 56, followed by ITX on day 84. Survival was greatest in isolated MHC class I mismatches, followed by isolated MHC class II mismatches. The shortest transplant survival was observed following full MHC mismatched ITX (P<0.05 vs. isolated MHC class I or II). Following recipient presensitization, islets in general showed reduced survival compared to naïve recipients. In this congenic rat model, islet transplant survival was significantly influenced by the degree of donor-recipient MHC matching, as well as by recipient presensitization. These data suggest that MHC matching might be useful in human islet transplantation.
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