Polycomb chromobox (Cbx) 7 modulates activation-induced CD4+ T cell apoptosis

Abstract

CD4+ T cell polarization plays a critical role in a number of immune disorders; the pathogenesis is unclear. Chromobox homolog 7 (Cbx7) is involved in the gene transcription of several cell types. This study aims to investigate the mechanism by which Cbx7 modulates the CD4+ T cell polarization. Expression of Cbx7 was assessed by quantitative RT-PCR and Western blotting. Apoptosis of CD4+ T cell was analyzed by flow cytometry. The FasL promoter methylation was evaluated by the methylation specific PCR. The results showed that CD4+ CD25− T cells express Cbx7 that was increased significantly after activation by exposing to anti-CD3/CD28 Ab, but suppressed by exposing to specific antigens. More apoptotic cells were detected in CD4+ T cells with the Cbx7 gene knockdown. Exposure to insulin-like growth factor-1 up regulated the expression of Cbx7 in CD4+ T cells. After antigen-specific TCR activation, Cbx7-deficient CD4+ T cells expressed more FasL and showed the FasL gene promoter hyper demethylation than wild CD4+ T cells. In addition, CD4+ T cells with overexpression of Cbx7 showed lower levels of FasL gene promoter demethylation. We conclude that CD4+ T cells express Cbx7; the latter prevents FasL expression and the activation-induced CD4+ T cell apoptosis.