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

  • Article
  • Immunology
  • Published:
Chinese Science Bulletin

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.

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Acknowledgments

This work was supported by the National Key Basic Research Program of China (2012CB917101), and the National Natural Science Foundation of China (30771968 and 81000920).

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Authors and Affiliations

  1. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Yi Tan, Xue Han, Xiaoran Wu, Qiao Xing & Shengdian Wang

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Yi Tan, Xue Han & Xiaoran Wu

  3. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Lieping Chen

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  1. Yi Tan
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  2. Xue Han
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  3. Xiaoran Wu
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  4. Qiao Xing
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  5. Lieping Chen
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  6. Shengdian Wang
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Correspondence to Shengdian Wang.

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Tan, Y., Han, X., Wu, X. et al. Anti-TOSO antibody treatment promotes T cell activation-induced cell death (AICD) in vitro and in vivo . Chin. Sci. Bull. 59, 1374–1385 (2014). https://doi.org/10.1007/s11434-014-0132-x

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  • DOI: https://doi.org/10.1007/s11434-014-0132-x

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