Stabilized β-catenin potentiates Fas-mediated T cell apoptosis

Zhaofeng Huang, Ruiqing Wang, Huimin Xie, Weirong Shang, Santhakumar Manicassamy, Zuoming Sun

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 Vβ8 + T cells. Using transgcnic mice expressing a stabilized β-catenin (β-cat Tg), we show here that β-catenin was able to enhance apoptosis of activated T cells by up-regulating Fas. In response to staphylococcal enterotoxin B stimulation, β-cat Tg mice exhibited accelerated deletion of CD4 +Vβ8 + T cells compared with wild type mice. Surface Fas levels were significantly higher on activated T cells obtained from β-cat Tg mice than that from wild type mice. Additionally, T cells from β-cat Tg mice w ere more sensitive to apoptosis induced by crosslinking Fas, activation-induced cell death, and to apoptosis induced by cytokine withdrawal. Lastly, β-catenin bound to and stimulated the Fas promoter. Therefore, our data demonstrated that the β-catenin pathway was able to promote the apoptosis of activated T cells in part via up-regulation of Fas.

Original languageEnglish (US)
Pages (from-to)6586-6592
Number of pages7
JournalJournal of Immunology
Volume180
Issue number10
Publication statusPublished - Dec 1 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Huang, Z., Wang, R., Xie, H., Shang, W., Manicassamy, S., & Sun, Z. (2008). Stabilized β-catenin potentiates Fas-mediated T cell apoptosis. Journal of Immunology, 180(10), 6586-6592.