INSERM U955, Institut Mondor de Recherche Biomédicale, 94010 Créteil, France.
J Immunol. 2013 Sep 15;191(6):3161-8. doi: 10.4049/jimmunol.1203547. Epub 2013 Aug 21.
The heterogeneity of human regulatory T cells (Tregs) may explain the discrepancies between studies on Tregs in physiology and pathology. Contrasting effects of IL-7 on the expansion and survival of human Tregs were reported. Therefore, we investigated the effects of IL-7 on the phenotype and function of well-characterized populations of human Tregs. We show that IL-7 signals via the CD127 receptor on naive, memory, and activated memory Tregs sorted from the blood of healthy donors, but it does not affect their proliferation. In contrast, IL-7 affects their suppressive capacities differently. This effect was modest on naive Tregs but was dramatic (90%) on memory Tregs. We provide evidence that IL-7 exerts a synergistic effect through downmodulation of the ectoenzyme CD39, which converts ATP to ADP/AMP, and an increase in ATP receptor P2X7. Both effects lead to an increase in the ATP-mediated effect, tipping the balance to favor Th17 conversion. Using an IL-7 therapeutic study, we show that IL-7 exerts the same effects in vitro and in vivo in HIV-infected individuals. Globally, our data show that IL-7 negatively regulates Tregs and contributes to increase the number of tools that may affect Treg function in pathology.
人类调节性 T 细胞（Tregs）的异质性可能解释了生理和病理状态下 Tregs 研究之间的差异。有报道称，IL-7 对人类 Tregs 的扩增和存活有相反的影响。因此，我们研究了 IL-7 对从健康供体血液中分选的具有特征性的人类 Tregs 群体的表型和功能的影响。我们发现，IL-7 通过 CD127 受体在幼稚、记忆和激活的记忆 Tregs 上发出信号，但不影响其增殖。相反，IL-7 以不同的方式影响它们的抑制能力。这种效应在幼稚 Tregs 上较小，但在记忆 Tregs 上则非常显著（90%）。我们提供的证据表明，IL-7 通过下调外切酶 CD39 发挥协同作用，CD39 将 ATP 转化为 ADP/AMP，并增加 ATP 受体 P2X7。这两种效应都导致 ATP 介导的效应增加，有利于 Th17 转化。通过一项 IL-7 治疗研究，我们表明 IL-7 在 HIV 感染者体内和体外均具有相同的作用。总的来说，我们的数据表明，IL-7 负调节 Tregs，并有助于增加可能影响病理中 Treg 功能的工具数量。
