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

P Pandiyan, L Zheng, S Ishihara, J Reed… - Nature …, 2007 - nature.com
P Pandiyan, L Zheng, S Ishihara, J Reed, MJ Lenardo
Nature immunology, 2007nature.com
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 …
Abstract
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.
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