CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells (Tregs) are highly sensitive to IL-2, one of the many cytokines produced during immune responses, for their development, survival and functions. Although the effects of IL-2 administration on Tregs in vivo are well characterized, the effects on Tregs elicited by IL-2 produced during an immune response have not been elucidated. Hence, in this study, Treg behaviour during IL-2–producing immune responses was explored using in vivo and in vitro murine systems. The use of murine mixed lymphocyte culture (MLC) revealed that a large proportion of Tregs increased in size, accompanied by both cell death and proliferation status. Further, these large Tregs, which were found to not recognize specific antigens, were observed in MLCs as being functionally activated by various cytokines, including IL-2, produced by antigen-specific T cells. This ‘bystander Treg activation’ was also observed in mice with graft-versus-host reactions (GvHRs). Alternatively, effector cells from Treg-depleted MLCs exhibited lower antigen-specific responses or higher cross-reactivity as compared to control MLCs with Tregs. Taken together, these results suggest that Tregs are activated by cytokines, mainly IL-2, released from T cells that are activated by a specific antigen. Subsequently, these activated bystander Tregs contribute to the fine-tuning of highly antigen-specific immune responses.

中文翻译：

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通过调节性T细胞对抗原特异性免疫反应的微调，该调节性T细胞通过独立于抗原识别和体液因子的机制激活

CD4 ⁺ CD25 ⁺ Foxp3 ⁺调节性T细胞（Tregs）对IL-2高度敏感，IL-2是免疫应答过程中产生的许多细胞因子之一，因为它们的发育，存活和功能。尽管已经很好地表征了IL-2施用对体内Treg的作用，但是尚未阐明免疫应答期间产生的IL-2引起的对Treg的作用。因此，在这项研究中，使用体内和体外鼠类系统探索了产生IL-2的免疫反应中Treg的行为。鼠类混合淋巴细胞培养物（MLC）的使用表明，大部分Tregs大小增加，并伴有细胞死亡和增殖状态。此外，在MLC中观察到发现这些大的Treg不能识别特定的抗原，并被抗原特异性T细胞产生的各种细胞因子（包括IL-2）功能性激活。在患有移植物抗宿主反应（GvHRs）的小鼠中也观察到这种“旁观者Treg激活”。备选地，与具有Treg的对照MLC相比，来自Treg耗尽的MLC的效应细胞表现出较低的抗原特异性应答或较高的交叉反应性。综上所述，这些结果表明，Treg被细胞因子（主要是IL-2）激活，该细胞因子从被特定抗原激活的T细胞中释放出来。随后，这些激活的旁观者Treg有助于高度抗原特异性免疫反应的微调。这些结果表明，Treg被细胞因子（主要是IL-2）激活，该细胞因子从被特定抗原激活的T细胞释放出来。随后，这些激活的旁观者Treg有助于高度抗原特异性免疫反应的微调。这些结果表明，Treg被细胞因子（主要是IL-2）激活，该细胞因子从被特定抗原激活的T细胞释放出来。随后，这些激活的旁观者Treg有助于高度抗原特异性免疫反应的微调。