Continuous requirement for the TCR in regulatory T cell function
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TLDR
It is demonstrated that inducible ablation of the TCR resulted in Treg cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of TReg cell signature genes or altered ability to sense and consume interleukin 2 (IL-2).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.read more
Citations
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References
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CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production
TL;DR: Data support the concept that the CD4+CD25+ T cells in normal mice may represent a distinct lineage of “professional” suppressor cells.
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CTLA-4 Control over Foxp3+ Regulatory T Cell Function
Kajsa Wing,Yasushi Onishi,Yasushi Onishi,Paz Prieto-Martin,Tomoyuki Yamaguchi,Makoto Miyara,Zoltan Fehervari,Takashi Nomura,Shimon Sakaguchi,Shimon Sakaguchi +9 more
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The inhibitory cytokine IL-35 contributes to regulatory T-cell function
Lauren W. Collison,Creg J. Workman,Timothy T. Kuo,Kelli L. Boyd,Yao Wang,Kate M. Vignali,Richard L. Cross,David Sehy,Richard S. Blumberg,Dario A. A. Vignali +9 more
TL;DR: IL-35 is identified as a novel inhibitory cytokine that may be specifically produced by Treg cells and is required for maximal suppressive activity.
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A function for interleukin 2 in Foxp3-expressing regulatory T cells
Jason D. Fontenot,Jason D. Fontenot,Jeffrey P. Rasmussen,Marc A. Gavin,Alexander Y. Rudensky +4 more
TL;DR: Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism, which seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.