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 T_reg cells induced apoptosis of effector CD4⁺ T cells in vitro and in vivo in a mouse model of inflammatory bowel disease. T_reg cells did not affect the early activation or proliferation of effector CD4⁺ T cells. Cytokines that signal through the common γ-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.