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

Yi Tan, Xue Han, Xiaoran Wu, Qiao Xing, Lieping Chen, Shengdian Wang

Research output: Contribution to journalArticle

Abstract

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 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 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 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.

Original languageEnglish (US)
Pages (from-to)1374-1385
Number of pages12
JournalChinese Science Bulletin
Volume59
Issue number13
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • AICD
  • Apoptosis
  • FcμR
  • IgM
  • TOSO

ASJC Scopus subject areas

  • General

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