Stabilized beta-catenin potentiates Fas-mediated T cell apoptosis.
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.
Huang
Zhaofeng
Z
Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
Wang
Ruiqing
R
Xie
Huimin
H
Shang
Weirong
W
Manicassamy
Santhakumar
S
Sun
Zuoming
Z
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D051176:beta Catenin; D019014:fas Receptor