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

Gang Du; Nuo Yang; Wenlin Gong; Yuan Fang; Jian He; Nuo Zhou; Xiaoling Lu; Yongxiang Zhao

doi:10.1016/j.yexcr.2017.02.036

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

Exp Cell Res. 2017 Jun 1;355(1):1-8. doi: 10.1016/j.yexcr.2017.02.036. Epub 2017 Feb 21.

Authors

Gang Du¹, Nuo Yang¹, Wenlin Gong², Yuan Fang³, Jian He³, Nuo Zhou², Xiaoling Lu⁴, Yongxiang Zhao⁵

Affiliations

¹ National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning 530021, China; The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; The Department of Immunology, Guangxi Medical University, Nanning 530021, China.
² National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning 530021, China.
³ National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning 530021, China; The Department of Immunology, Guangxi Medical University, Nanning 530021, China.
⁴ National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning 530021, China; The Department of Immunology, Guangxi Medical University, Nanning 530021, China. Electronic address: luwuliu@163.com.
⁵ National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Nanning 530021, China; The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; The Department of Immunology, Guangxi Medical University, Nanning 530021, China. Electronic address: yongxiang_zhao@126.com.

PMID: 28232114
DOI: 10.1016/j.yexcr.2017.02.036

Abstract

Background: To 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.

Methods: A 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⁺ T_em 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.

Results: Adoptive 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.

Conclusions: The 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.

Keywords: Allograft rejection; CD8(+) effector memory T cells; CD8(+) memory T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Animals
CD8-Positive T-Lymphocytes / immunology*
Cytokines / biosynthesis*
Cytokines / immunology*
Graft Rejection / immunology*
Heart Transplantation*
Immunologic Memory*
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Transplantation, Homologous

Substances

Cytokines