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 language | English (US) |
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Pages (from-to) | 1374-1385 |
Number of pages | 12 |
Journal | Chinese Science Bulletin |
Volume | 59 |
Issue number | 13 |
DOIs | |
State | Published - 2014 |
Externally published | Yes |
Keywords
- AICD
- Apoptosis
- FcμR
- IgM
- TOSO
ASJC Scopus subject areas
- General