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-catTg), 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-catTg 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-catTg mice than that from wild type mice. Additionally, T cells from β-catTg 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
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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