Stabilized beta-catenin potentiates Fas-mediated T cell apoptosis

• Published in: The Journal of immunology (1950) Vol. 180; no. 10; pp. 6586 - 6592
• Main Authors: Huang, Zhaofeng, Wang, Ruiqing, Xie, Huimin, Shang, Weirong, Manicassamy, Santhakumar, Sun, Zuoming
• Format: Journal Article
• Language: English
• Published: United States 15.05.2008
• Subjects: Animals; Apoptosis - immunology; beta Catenin - genetics; beta Catenin - metabolism; fas Receptor - metabolism; Flow Cytometry; Humans; Immunoprecipitation; Jurkat Cells; Lymphocyte Activation - immunology; Mice; Mice, Transgenic; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Up-Regulation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.180.10.6586

In response to Ag stimulation, Ag-specific T cells proliferate and accumulate in the peripheral lymphoid tissues. To avoid excessive T cell accumulation, the immune system has developed mechanisms to delete clonally expanded T cells. Fas/FasL-mediated apoptosis plays a critical role in the deletion of activated peripheral T cells, which is clearly demonstrated by superantigen (staphylococcal enterotoxin B)-induced deletion of Vbeta8(+) T cells. Using transgenic mice expressing a stabilized beta-catenin (beta-cat(Tg)), we show here that beta-catenin was able to enhance apoptosis of activated T cells by up-regulating Fas. In response to staphylococcal enterotoxin B stimulation, beta-cat(Tg) mice exhibited accelerated deletion of CD4(+)Vbeta8(+) T cells compared with wild type mice. Surface Fas levels were significantly higher on activated T cells obtained from beta-cat(Tg) mice than that from wild type mice. Additionally, T cells from beta-cat(Tg) mice were more sensitive to apoptosis induced by crosslinking Fas, activation-induced cell death, and to apoptosis induced by cytokine withdrawal. Lastly, beta-catenin bound to and stimulated the Fas promoter. Therefore, our data demonstrated that the beta-catenin pathway was able to promote the apoptosis of activated T cells in part via up-regulation of Fas.