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

Publication date: Available online 21 February 2017
Source:Experimental Cell Research
Author(s): Gang Du, Nuo Yang, Wenlin Gong, Yuan Fang, Jian He, Nuo Zhou, Xiaoling Lu, Yongxiang Zhao
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⁺ 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.



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