CD8效应记忆T细胞可能通过激活炎性细胞因子的表达，诱导小鼠同种异体心脏再次移植的急性排斥反应。
CD8 effector memory T cells induce acute rejection of allogeneic heart retransplants in mice possibly through activating expression of inflammatory cytokines.
作者信息
Du Gang, Yang Nuo, Gong Wenlin, Fang Yuan, He Jian, Zhou Nuo, Lu Xiaoling, Zhao Yongxiang
机构信息
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.
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.
出版信息
Exp Cell Res. 2017 Jun 1;355(1):1-8. doi: 10.1016/j.yexcr.2017.02.036. Epub 2017 Feb 21.
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 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.
背景
研究CD8记忆T（Tm）细胞和CD8效应记忆T（Tem）细胞对小鼠同种异体心脏再次移植结果的影响。
方法
使用皮肤移植模型生成致敏的脾CD8 Tem细胞，将其注入BALB/c小鼠体内。注入一周后，对BALB/c小鼠进行腹腔内同种异体心脏移植。从移植前一天开始通过腹腔注射给予环孢素A，以阻止移植心脏的免疫排斥反应。通过监测移植心脏的存活情况、效应记忆CD8 T细胞向心肌的浸润以及血清中炎性细胞因子的表达，来检测致敏CD8 T细胞对同种异体心脏移植排斥反应的影响。
结果
移植前过继转移致敏的CD8 Tem细胞诱导了急性排斥反应，降低了移植心脏的存活率。排斥反应伴随着CD8 Tem细胞浸润到移植的心肌组织中。此外，注入致敏的CD8 Tem细胞导致移植心脏中IL-2和IFN-γ的表达明显增加，TGF-β的表达降低，以及血清中IFN-γ和CXCL-9的水平升高。
结论
注入致敏的CD8 Tem细胞通过调节包括CXCL-9、IL-2和INF-γ在内的炎性细胞因子的表达，诱导了急性移植排斥反应并降低了移植心脏的存活率。环孢素A对致敏的CD8 Tem细胞诱导的移植排斥反应没有治疗作用。
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