Anti-TOSO antibody treatment promotes T cell activation-induced cell death(AICD) in vitro and in vivo  

作　　者：Yi Tan Xue Han Xiaoran Wu Qiao Xing Lieping Chen Shengdian Wang 

机构地区：[1]Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences [2]University of Chinese Academy of Sciences [3]Department of Immunobiology, Yale University School of Medicine

出　　处：《Chinese Science Bulletin》2014年第13期1374-1385,共12页

基　　金：supported by the National Key Basic Research Program of China(2012CB917101);the National Natural Science Foundation of China(30771968 and 81000920)

摘　　要：T cell activation-induced cell death(AICD),that involves the induction of Fas-mediated apoptosis,is very important for the maintenance of immune homeostasis.TOSO was firstly described as an inhibitor of Fasmediated apoptosis and overexpressed in chronic lymphocytic leukemia.Recently,TOSO was identified as IgM FcR.In this study,we produced anti-TOSO monoclonal antibody(mAb)that could block the binding of IgM to TOSO and found that T cell apoptosis is negatively correlated with TOSO expression during T cell activation.Treatment of activated T cells with anti-TOSO blocking mAb promoted T cell AICD in in vitro AICD model,and treatment of xenogeneic-GVHD mice with the antibody also increased the sensitivity of activated T cells to Fasinduced apoptosis,which was accompanied by reduction of c-FLIPL expression and up-regulation of AP-1 complex.In summary,our data indicate the anti-apoptotic effect of TOSO in T cell AICD and open up new therapeutic prospects for the treatment of hematologic malignancies and immune disorders.T cell activation-induced cell death （AICD）, that involves the induction of Fas-mediated apoptosis, is very important for the maintenance of immune homeosta- sis. TOSO was firstly described as an inhibitor of Fas- mediated apoptosis and overexpressed in chronic lymphocytic leukemia. Recently, TOSO was identified as IgM FcR. In this study, we produced anti-TOSO monoclonal antibody （mAb） that could block the binding of IgM to TOSO and found that T cell apoptosis is negatively cor- related with TOSO expression during T cell activation. Treatment of activated T cells with anti-TOSO blocking mAb promoted T cell AICD in in vitro AICD model, and treatment of xenogeneic-GVHD mice with the antibody also increased the sensitivity of activated T cells to Fas- induced apoptosis, which was accompanied by reduction of c-FLIPL expression and up-regulation of AP-1 complex. In summary, our data indicate the anti-apoptotic effect of TOSO in T cell AICD and open up new therapeutic prospects for the treatment of hematologic malignancies and immune disorders.

关 键 词：T细胞活化 单克隆抗体 细胞死亡 治疗 诱导 体外 FAS介导 淋巴细胞白血病 

分 类 号：R733.7[医药卫生—肿瘤]