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

A key issue in mammalian immunology is how CD4(+) CD25(+) Foxp3(+) regulatory T cells ( T-reg 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 gamma- chain suppressed T-reg cell- induced apoptosis. T-reg cell-induced effector CD4(+) T cell death required the proapoptotic protein Bim, and effector CD4(+) T cells incubated with T-reg 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 T-reg cells inhibit effector T cell responses.