Arsenic trioxide inhibits accelerated allograft rejection mediated by alloreactive CD8+ memory T cells and prolongs allograft survival time

• We build alloreactive CD8+ memory T (Tm) cell-mediated allograft rejection model in nude mice.
• The immunosuppressive effect of arsenic trioxide (As2O3) is evaluated.
• As2O3 inhibits allograft rejection mediated by suppress CD8+ Tm cell respond.

CD8+ memory T (Tm) cells are a significant barrier to transplant tolerance induction in alloantigen-primed recipients, and are insensitive to existing clinical immunosuppressants. Here, we studied the inhibition of CD8+ Tm cells by arsenic trioxide (As2O3) for the first time. Alloantigen-primed CD8+ Tm cells were transferred to T cell immunodeficient nude mice. The mice were subjected to heart allotransplantation, and treated with As2O3. The transplant survival time was determined, and the inhibitory effects of As2O3 on CD8+ Tm cell-mediated immune rejection were assessed through serological studies and inspection of the transplanted heart and lymphoid organs. We found that As2O3 treatment prolonged the mean survival time of the graft and reduced the number of CD8+ Tm cells in the spleen and lymph nodes. The expression of the genes encoding interleukin (IL)-2, and IFN-γ was reduced, while expression of IL-10 and transforming growth factor-β was increased in the transplant. Our findings show that As2O3 treatment inhibits allograft rejection mediated by alloreactive CD8+ Tm cells in the mouse heart transplantation model.