CD8+ effector memory T cells induce acute rejection of allogeneic heart retransplants in mice possibly through activating expression of inflammatory cytokines

Abstract

BackgroundTo investigate the effects of CD8+ memory T (Tm) cells and CD8+ effector memory T (Tem) cells on the results of allogeneic heart retransplantations performed in mice. MethodsA skin transplantation model was used to generate sensitized splenic CD8+ Tem cells for infusion into BALB/c mice. One week after infusion, the BALB/c mice underwent allogeneic heart transplantation in the abdominal cavity. Cyclosporin A was administered via intraperitoneal injection starting one day prior to transplantation to arrest immunological rejection of the transplanted heart. The effects of sensitized CD8+ Tem cells on allogeneic heart graft rejection were examined by monitoring survival of the transplanted hearts, the infiltration of effector memory CD8+ T cells into myocardium, and expressions of inflammatory cytokines in blood serum. ResultsAdoptive transfer of sensitized CD8+ Tem cells prior to transplantation induced an acute rejection response which decreased the survival of transplanted hearts. The rejection response was accompanied by an infiltration of CD8+ Tem cells into the transplanted myocardial tissue. Additionally, infusion of sensitized CD8+ Tem cells induced markedly increased expressions of IL-2 and IFN-γ, and decreased expression of TGF-β in the transplanted hearts, as well as higher levels of IFN-γ and CXCL-9 in blood serum. ConclusionsThe infusion of sensitized CD8+ Tem cells induced an acute graft rejection response and decreased the survival of grafted hearts by regulating the expressions of inflammatory cytokines including CXCL-9, IL-2, and INF-γ. Cyclosporin A had no therapeutic effect on the graft rejection response induced by sensitized CD8+ Tem cells.