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 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.
Pandiyan
Pushpa
P
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zheng
Lixin
L
Ishihara
Satoru
S
Reed
Jennifer
J
Lenardo
Michael J
MJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit