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 nonlethal 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, Treg 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.

FoxP3 ⁺调节性 T 细胞 (Treg) 控制炎症并维持粘膜稳态，但人们对它们在感染期间的功能知之甚少。Th1、Th2 和 Th17 细胞可通过主转录因子 (TF) T-bet、GATA3 和 RORγT 进行识别；Tregs 也表达这些 TF。虽然 T-bet ⁺ Tregs 可以选择性地抑制 Th1 细胞，但尚不清楚不同的 Treg 群体是否可以改变 Th 偏差。为了解决这个问题，我们使用肠杆菌血清型鼠伤寒沙门氏菌来诱导非致死性结肠炎。感染后，我们在总 CD4 T 细胞内观察到早期结肠 Th17 反应，随后是 Th1 偏倚。早期 Th17 反应，其中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 ⁺ Tregs 的增加。后来，Th1 细胞和 RORγT ⁺ Tregs 占主导地位。这种相互动态可能表明 Tregs 选择性地抑制 Th 细胞，从而形成免疫反应。感染后 1-2 天 Treg 耗竭将早期 Th17 反应转变为 Th1 偏倚；然而，感染后 6-7 天 Treg 耗尽消除了 Th1 偏差。因此，Tregs 对于早期的 Th17 反应和之后的最大 Th1 反应是必需的。这些数据表明，Tregs 塑造了整体组织 CD4 T 细胞反应，并突出了 Tregs 亚群用于靶向治疗方法的潜力。