Center for Regenerative Therapies Dresden, Dresden University of Technology, 01307 Dresden, Germany.
J Immunol. 2012 Dec 15;189(12):5649-58. doi: 10.4049/jimmunol.1201286. Epub 2012 Nov 5.
CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) control the activation and expansion of alloreactive and autoreactive T cell clones. Because uncontrolled activation and expansion of autoreactive T cells occur in an IL-7-rich environment, we explored the possibility that IL-7 may affect the function of Treg. We show that the functional high-affinity IL-7R is expressed on both naive and memory Tregs, and exposure to IL-7 results in STAT-5 phosphorylation. Naive, but not memory, Tregs proliferated greatly and acquired a memory phenotype in the setting of a suppression assay when IL-7 was present. Importantly, the presence of IL-7 abrogated the capacity of Tregs to suppress proliferation of conventional T cells in response to TCR activators, including alloantigens and autoantigens. Removal of IL-7 restored the suppressive function of Tregs. Preblocking of the IL-7R on the Tregs also restored suppressor function, indicating that IL-7 directly affected Treg function. Thus, prolonged periods of homeostatic expansion can temporarily release natural regulatory brakes on T cells, thereby providing an additional mechanism for activating and expanding alloreactive and autoreactive T cells.
CD4(+)CD25(+)FOXP3(+)调节性 T 细胞（Tregs）控制同种反应性和自身反应性 T 细胞克隆的激活和扩增。因为在富含白细胞介素-7（IL-7）的环境中，自身反应性 T 细胞的不受控制的激活和扩增会发生，所以我们探讨了 IL-7 可能影响 Treg 功能的可能性。我们表明，高亲和力的 IL-7R 表达在幼稚和记忆 Tregs 上，并且暴露于 IL-7 导致 STAT-5 磷酸化。在抑制测定中，当存在 IL-7 时，幼稚但不是记忆 Tregs 大量增殖并获得记忆表型。重要的是，IL-7 的存在消除了 Tregs 抑制 TCR 激活剂（包括同种抗原和自身抗原）引起的常规 T 细胞增殖的能力。去除 IL-7 恢复了 Tregs 的抑制功能。在 Tregs 上预先阻断 IL-7R 也恢复了抑制功能，表明 IL-7 直接影响 Treg 功能。因此，长期的稳态扩增可以暂时释放 T 细胞上的天然调节刹车，从而为激活和扩增同种反应性和自身反应性 T 细胞提供了另一种机制。
