CD4+ T Cells Are Sufficient to Elicit Allograft Rejection and Major Histocompatibility Complex Class I Molecule Is Required to Induce Recurrent Autoimmune Diabetes After Pancreas Transplantation in Mice

Background. We characterized the role of T cell subsets and major histocompatibility complex molecules in allograft rejection and recurrence of autoimmune diabetes. Methods. Adoptive cell transfer and vascularized segmental pancreas transplantation were performed in mice. Results. In an alloimmune response model, transfer of nondiabetic CD4+, but not CD8+ T cells, elicited pancreas allograft rejection in streptozotocin (STZ)-induced diabetic NOD/scid mice. Pancreas allografts were acutely rejected in STZ-induced diabetic NOD/&bgr;2m−/− mice (confirmed the absence of major histocompatibility complex [MHC] class I and CD8+ T cells) and permanently accepted in NOD/CIIT−/− mice (confirmed the absence of MHC class II and CD4+ T cells). The results suggest that rejection of pancreas allograft is CD4-dependent and MHC class I-independent. In the autoimmune diabetes model, whole spleen cells obtained from diabetic NOD mice induced autoimmune diabetes in NOD/scid and NOD/CIIT−/− mice, but the onset of diabetes was delayed in NOD/&bgr;2m−/− mice. However, the purified diabetic T cells failed to elicit autoimmune diabetes in NOD/&bgr;2m−/− mice. NOD/scid and NOD/CIIT−/− pancreas grafts were acutely destroyed whereas four of six NOD/&bgr;2m−/− pancreas grafts were permanently accepted in autoimmune diabetic NOD mice. Conclusion. CD4+ T cells are sufficient for the induction of allograft rejection, and MHC class I molecule is required to induce recurrent autoimmune diabetes after pancreas transplantation in mice.