Abstract

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 -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.

1. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
2. Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Correspondence to: Michael J Lenardo¹ e-mail: lenardo@nih.gov

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