Arsenic Trioxide Inhibits The Reactivity Of Allograft Memory CD8~+T Cell-mediated Transplant Rejection

Objective:Memory T (Tm) cells are a significant barrier to the induction of transplant tolerance. Therefore, inhibiting the generation of these cells is a key to preventing accelerated rejection and prolonging graft survival.Methods:For this purpose, a model was constructed through adoptive transfer of CD8+Tm cells into T cell-immunodeficient nude mice. Mice were then subjected to heart transplantation and arsenic trioxide (AS2O3) treatment. The survival time of the transplant was determined, and the inhibitory effects of As2O3on CD8+Tm cell-mediated transplant rejection were reassessed by inspecting the transplant and lymphoid organs and performing serological tests.Results:As2O3treatment extended the mean survival time of the transplant and reduced the inflammatory cell infiltration in the transplant and the number of CD8+Tm cells in the spleen and lymph nodes. The mRNA expression of interleukin (IL)-2and interferon-y was reduced in the transplant, while the mRNA expression of IL-10and transforming growth factor-β was increased.Conclusion:Our findings show that As2O3treatment inhibits the proliferation and immune killing of CD8+Tm cells and prolongs the graft survival in this nude mouse model of heart transplantation.