Role of MS4a4B in regulation of T cell apoptosis (104.20)

Abstract

Abstract MS4a4B is a membrane protein that highly expressed in T cells. We have demonstrated previously that MS4a4B has an inhibitory role in T cell proliferation. Interestingly, a decreased level of MS4a4B is associated with apoptotic T cells. In this study, we further analyzed the role of MS4a4B in T cell proliferation and apoptosis. We co-cultured MS4a4B+ EL4 cells (GFP+) with MS4a4B- EL4 cells (GFP-) and compared cell proliferation by flow cytometry. We found that MS4a4B inhibited EL4 cell proliferation during the early stage of co-culture. However, the percentage of MS4a4B+ EL4 cells was enhanced, suggesting that MS4a4B prolonged EL4 cell survival. To determine if MS4a4B expression reduced apoptosis in EL4 cells, we analyzed apoptotic cells during MS4a4B+/MS4a4B- cell co-culture. The results showed that the apoptosis percentage in MS4a4B+ EL4 cells was markedly lower than in MS4a4B- EL4 cells. To determine whether MS4a4B protected T cells from activation-induced cell death (AICD), we knocked down MS4a4B expression in mouse T cell line (T32 cells) and primary T cells by MS4a4B shRNA vector and MS4a4B siRNA. Knockdown of MS4a4B promoted anti-CD3/anti-CD28-induced apoptosis in T32 cells and primary T cells. Machinery analysis showed that over-expression of MS4a4B decreased the activity of caspase 3/7, caspase 8 and caspase 9. Our data suggest that MS4a4B not only has an inhibitory role in T cell proliferation but also plays a role in regulation of T cell apoptosis.