FoxP3⁺ regulatory T cells (Tregs) control inflammation and maintain mucosal homeostasis, but their functions during infection are poorly understood. Th1, Th2 and Th17 cells can be identified by master transcription factors (TFs) T-bet, GATA3 and RORγT; Tregs also express these TFs. While T-bet⁺ Tregs can selectively suppress Th1 cells, it is unclear whether distinct Treg populations can alter Th bias. To address this, we used Salmonella enterica serotype Typhimurium to induce non-lethal colitis. Following infection, we observed an early colonic Th17 response within total CD4 T cells, followed by a Th1 bias. The early Th17 response, which contains both Salmonella-specific and non-Salmonella-specific cells, parallels an increase in T-bet⁺ Tregs. Later, Th1 cells and RORγT⁺ Tregs dominate. This reciprocal dynamic may indicate that Tregs selectively suppress Th cells, shaping the immune response. Treg depletion 1-2 days post-infection shifted the early Th17 response to a Th1 bias; however, depletion 6-7 days post-infection abrogated the Th1 bias. Thus, Tregs are necessary for the early Th17 response, and for a maximal Th1 response later. These data show that Tregs shape the overall tissue CD4 T cell response and highlight the potential for subpopulations of Tregs to be used in targeted therapeutic approaches.

中文翻译：

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沙门氏菌感染后调节性T细胞控制CD4 T细胞的动态和位点特异性极化

FoxP3 ⁺调节性T细胞（Tregs）控制炎症并维持粘膜稳态，但是人们对其在感染过程中的功能了解甚少。Th1，Th2和Th17细胞可以通过主转录因子T-bet，GATA3和RORγT进行鉴定；Treg也表达这些TF。尽管T-bet ⁺ Tregs可以选择性抑制Th1细胞，但尚不清楚不同的Treg群体是否可以改变Th偏倚。为了解决这个问题，我们使用了沙门氏菌血清型鼠伤寒沙门氏菌来诱发非致死性结肠炎。感染后，我们在总CD4 T细胞内观察到早期的结肠Th17反应，然后出现Th1偏倚。Th17早期反应，包含沙门氏菌特异性和非沙门氏菌-特异性细胞，平行于T-bet ⁺ Treg的增加。后来，Th1细胞和RORγT ⁺ Treg占据主导地位。这种相互关系的动态可能表明，Tregs选择性抑制Th细胞，从而形成免疫应答。感染后1-2天的Treg耗竭使Th17早期反应转变为Th1偏倚。但是，感染后6-7天的耗竭消除了Th1偏倚。因此，Tregs对于早期的Th17应答和后来的最大Th1应答都是必需的。这些数据表明，Tregs可影响整个组织CD4 T细胞的反应，并突出了将Tregs亚群用于靶向治疗方法的潜力。