MHC-mismatched islet allografts are vulnerable to autoimmune recognition in vivo

摘要: When transplanted into type 1a diabetic recipients, islet allografts are subject both to conventional allograft immunity and, presumably, recurrent autoimmune (islet-specific) pathogenesis. Importantly, CD4 T cells play a central role in rejection and disease recurrence leading the destruction of syngeneic transplants NOD mice. However, it is unclear how host MHC class II (I-A(g7))-restricted, autoreactive may also contribute recognition allogeneic grafts that express disparate molecules. We hypothesized islet-specific can target MHC-mismatched for via "indirect" (host APC-dependent) pathway Ag recognition. To test this hypothesis, we determined whether NOD-derived, (BDC-2.5 TCR transgenic cells) could damage islets vivo independent immunity. Results demonstrate BDC-2.5 vigorously destroy II-disparate established NOD.scid recipients. Tissue injury tissue-specific donor-type islet, but not thyroid same recipient. Furthermore, acutely II-deficient vivo, indicating pathogenesis be completely donor expression. Taken together, these findings indicate vulnerable triggered by cells, presumably through indirect autoantigen vivo.