Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX.
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, China.
J Exp Med. 2021 Jan 4;218(1). doi: 10.1084/jem.20200030.
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.
除了 Foxp3+ CD4+ 调节性 T 细胞（CD4+ Treg 细胞），Foxp3- CD8+ 调节性 T 细胞（CD8+ Treg 细胞）对于维持免疫耐受也很重要。然而，特异性控制 CD8+但不控制 CD4+Treg 细胞的分子程序在很大程度上是未知的。在这里，我们证明了 T 细胞中同时破坏 TGF-β 受体和转录因子 Eomesodermin（Eomes）会导致致命的自身免疫，这是由于 CD8+但不是 CD4+Treg 细胞的特定缺陷。此外，TGF-β 信号维持调节性细胞身份，而 Eomes 控制 CD8+Treg 细胞的滤泡位置。TGF-β 信号和 Eomes 共同协调促进 CD8+Treg 细胞的稳态。总之，我们已经确定了一个专门为 CD8+Treg 细胞设计的独特分子程序。
