title: Continuous requirement for the TCR in regulatory T cell function.
abstract: Foxp3(+) regulatory T cells (T(reg) cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of T(reg) cells, the role of TCR signaling in T(reg) cell function remains largely unknown. Here we demonstrated that inducible ablation of the TCR resulted in T(reg) cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of T(reg) cell signature genes or altered ability to sense and consume interleukin 2 (IL-2). Instead, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated T(reg) cell transcriptional signature. Our results reveal a critical role for the TCR in the suppressor capacity of T(reg) cells.
authors.affiliation: 1] Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. [2] Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Levine
authors.affiliation: 1] Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. [2] Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Arvey
authors.affiliation: 1] Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. [2] Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: 1] Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. [2] Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. [3] Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004167:Diphtheria Toxin / Q000008:administration & dosage; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C476399:Cd44 protein, mouse; D004167:Diphtheria Toxin; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018960:Hyaluronan Receptors; D018793:Interleukin-13; D007376:Interleukin-2; D019394:Ki-67 Antigen; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D013629:Tamoxifen; D015847:Interleukin-4; D007371:Interferon-gamma