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 ap...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.展开更多
基金supported by the National Key Basic Research Program of China(2012CB917101)the National Natural Science Foundation of China(30771968 and 81000920)
文摘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.
