Wyss Lena, Stadinski Brian D, King Carolyn G, Schallenberg Sonja, McCarthy Nicholas I, Lee Jun Young, Kretschmer Karsten, Terracciano Luigi M, Anderson Graham, Surh Charles D, Huseby Eric S, Palmer Ed
Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Department of Nephrology, University Hospital Basel and University of Basel, Basel, Switzerland.
Nat Immunol. 2016 Sep;17(9):1093-101. doi: 10.1038/ni.3522. Epub 2016 Aug 1.
The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) Treg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) Tconv cells into induced Treg cells (iTreg cells). Although Foxp3-deficient (Scurfy) mice lacked Treg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells zsuper> T cells infiltrated the skin, whereas Scurfy Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of Treg cells into distinct subsets with non-overlapping regulatory activities.
调节性T细胞（Treg细胞）控制淋巴细胞稳态的方式尚未完全明确。我们鉴定出了两个具有不同程度自身反应性和独特调节功能的Treg细胞群体。我们发现，糖皮质激素诱导肿瘤坏死因子受体高表达（GITR(hi)）、程序性死亡受体1高表达（PD-1(hi)）、CD25高表达（Triple(hi)）的Treg细胞具有高度自身反应性，并控制外周淋巴结中的淋巴细胞增殖。GITR低表达（GITR(lo)）、PD-1低表达（PD-1(lo)）、CD25低表达（Triple(lo)）的Treg细胞自身反应性较低，并通过促进CD4(+)辅助性T细胞（Tconv细胞）转化为诱导性Treg细胞（iTreg细胞）来限制结肠炎的发展。尽管Foxp3缺陷（Scurfyfy）小鼠缺乏Treg细胞，但它们含有类似Triple(hi)和类似Triple(lo)的CD4(+) T细胞。Scurfy Triple(hi) CD4(+) T细胞浸润皮肤，而Scurfy Triple(lo) CD4(+) T细胞则诱发结肠炎和消瘦病。这些发现表明，T细胞抗原受体对自身抗原的亲和力驱动Treg细胞分化为具有非重叠调节活性的不同亚群。
