CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells

Pushpa Pandiyan, Lixin Zheng, Satoru Ishihara, Jennifer Reed, Michael J. Lenardo

Research output: Contribution to journalArticlepeer-review

785 Citations (Scopus)


A key issue in mammalian immunology is how CD4+ CD25+ Foxp3+ regulatory T cells (Treg cells) suppress immune responses. Here we show that Treg cells induced apoptosis of effector CD4+ T cells in vitro and in vivo in a mouse model of inflammatory bowel disease. Treg cells did not affect the early activation or proliferation of effector CD4+ T cells. Cytokines that signal through the common γ-chain suppressed Treg cell-induced apoptosis. Treg cell-induced effector CD4+ T cell death required the proapoptotic protein Bim, and effector CD4+ T cells incubated with Treg cells showed less activation of the prosurvival kinase Akt and less phosphorylation of the proapoptotic protein Bad. Thus, cytokine deprivation-induced apoptosis is a prominent mechanism by which Treg cells inhibit effector T cell responses.

Original languageEnglish
Pages (from-to)1353-1362
Number of pages10
JournalNature Immunology
Issue number12
Publication statusPublished - 12-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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