In addition to Foxp3+ CD4+ regulatory T cells (CD4+ T reg cells), Foxp3− CD8+ regulatory T cells (CD8+ T reg cells) are critical to maintain immune tolerance. However, the molecular programs that specifically control CD8+ but not CD4+ T reg cells are largely unknown. Here, we demonstrate that simultaneous disruption of both TGF-β receptor and transcription factor Eomesodermin (Eomes) in T cells results in lethal autoimmunity due to a specific defect in CD8+ but not CD4+ T reg cells. Further, TGF-β signal maintains the regulatory identity, while Eomes controls the follicular location of CD8+ T reg cells. Both TGF-β signal and Eomes coordinate to promote the homeostasis of CD8+ T reg cells. Together, we have identified a unique molecular program designed for CD8+ T reg cells.
TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells
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Shruti Mishra, Wei Liao, Yong Liu, Ming Yang, Chaoyu Ma, Haijing Wu, Ming Zhao, Xin Zhang, Yuanzheng Qiu, Qianjin Lu, Nu Zhang; TGF-β and Eomes control the homeostasis of CD8+ regulatory T cells. J Exp Med 4 January 2021; 218 (1): e20200030. doi: https://doi.org/10.1084/jem.20200030
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