An essential role for the IL-2 receptor in Tregcell function.
Regulatory T cells (Tregcells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Tregcells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Tregcell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Tregcells. Using genetic gain- and loss-of-function approaches, we found that capture of IL-2 was dispensable for the control of CD4+T cells but was important for limiting the activation of CD8+T cells, and that IL-2R-dependent activation of the transcription factor STAT5 had an essential role in the suppressor function of Tregcells separable from signaling via the T cell antigen receptor.
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Takatoshi
T
Chinen
Immunology Discovery, Biogen, Cambridge, MA, USA.
Arun K
AK
Kannan
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Andrew G
AG
Levine
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Xiying
X
Fan
Herbert Irving Comprehensive Cancer Center, Department of Pathology and Cell Biology, and Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
Ulf
U
Klein
Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Ye
Y
Zheng
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Institute for Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany.
Georg
G
Gasteiger
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Yongqiang
Y
Feng
Exploratory Biology, Juno Therapeutics, Seattle, WA, USA.
Jason D
JD
Fontenot
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alexander Y
AY
Rudensky
D000818:Animals; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D056747:Immunomodulation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor