Islet allograft destruction in NOD mice is independent of donor MHC expression
Journal of Immunology(2014)
摘要
Abstract It is unclear whether autoimmune disease recurrence overlaps with allograft immunity in the autoimmune diabetic recipient of a pancreatic islet transplant. We grafted autoimmune NOD mice with either syngeneic NOD or allogeneic C57Bl/6 (B6) islets that were genetically deficient in MHC class I, MHC class II, or both MHC class I and MHC class II. NOD.RAG-/- or MHC II-deficient NOD islets were acutely destroyed, but depletion of CD8+ T cells significantly prolonged graft survival. Most NOD MHC I-deficient or MHC I/II-deficient islets survived long-term (>100 d). In contrast, B6 allografts that were MHC sufficient, or deficient in MHC class I, class II, or both were acutely rejected. Allograft rejection was CD4+ T cell dependent and CD8+ T cell independent. Of note, islet allograft rejection in non-autoimmune recipients requires donor islet MHC I or MHC II expression. Lastly, autoimmune disease recurrence was accelerated by depletion of CD25+ cells. We hypothesize that autoimmune disease recurrence is primarily a CD8+ T cell mediated response restricted by donor MHC class I molecules and is delayed by CD4+CD25+ regulatory T cells. In contrast, results suggest that CD4+ T cells play a predominant role in allograft rejection in the autoimmune recipient. We propose the lack of down-regulation of the anti-allograft response and the presence of primed autoreactive T cells synergize to produce the rapid allograft rejection observed in the autoimmune islet transplant recipient.
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