Regulatory T cells (Tregs) expressing the transcription factor Foxp3 play a critical role in the control of immune homeostasis including the regulation of humoral immunity. Recently, it has become clear that a specialized subset of Tregs, T‐follicular regulatory cells (Tfr), have a particular role in the control of T‐follicular helper (Tfh) cell‐driven germinal center (GC) responses. Following similar differentiation signals as received by Tfh, Tfr gain expression of characteristic chemokine receptors and transcription factors such as CXCR5 and BCL6 allowing them to travel to the B‐cell follicle and deliver in situ suppression. It seems clear that Tfr are critical for the prevention of autoimmune antibody induction. However, their role in the control of foreign antigen‐specific antibody responses appears more complex with various reports demonstrating either increased or decreased antigen‐specific antibody responses following inhibition of Tfr function. Due to their recent discovery, our understanding of Tfr formation and function still has many gaps. In this review, we discuss our current knowledge of both Tregs and Tfr in the context of humoral immunity and how these cells might be manipulated in order to better control vaccine responses.

中文翻译：

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Treg 和 Tfr 控制外来 Ag 特异性 Ab 反应。

表达转录因子 Foxp3 的调节性 T 细胞 (Tregs) 在控制免疫稳态（包括调节体液免疫）中起关键作用。最近，很明显，Tregs 的一个特殊亚群，T 滤泡调节细胞 (Tfr)，在控制 T 滤泡辅助 (Tfh) 细胞驱动的生发中心 (GC) 反应中具有特殊作用。在 Tfh 接收到类似的分化信号后，Tfr 获得特征趋化因子受体和转录因子（如 CXCR5 和 BCL6）的表达，使它们能够进入 B 细胞滤泡并进行原位抑制。似乎很清楚 Tfr 对于预防自身免疫抗体的诱导至关重要。然而，它们在控制外来抗原特异性抗体反应中的作用似乎更复杂，各种报告表明抑制 Tfr 功能后抗原特异性抗体反应增加或减少。由于他们最近的发现，我们对 Tfr 形成和功能的理解仍有许多空白。在这篇综述中，我们讨论了我们目前在体液免疫背景下对 Tregs 和 Tfr 的了解，以及如何操纵这些细胞以更好地控制疫苗反应。