Islet allograft destruction in NOD mice is independent of donor MHC expression (TRAN3P.870)

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (1_Supplement), p.202-202.9
• Main Authors: Burrack, Adam, Beilke, Joshua, Kupfer, Tinalyn, Beard, K. Scott, Coulombe, Marilyne, Gill, Ronald
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.202.9

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.