Sage Peter T, Ron-Harel Noga, Juneja Vikram R, Sen Debattama R, Maleri Seth, Sungnak Waradon, Kuchroo Vijay K, Haining W Nicholas, Chevrier Nicolas, Haigis Marcia, Sharpe Arlene H
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.
Nat Immunol. 2016 Dec;17(12):1436-1446. doi: 10.1038/ni.3578. Epub 2016 Oct 3.
Follicular regulatory T cells (T cells) inhibit follicular helper T cell (T cell)-mediated antibody production. The mechanisms by which T cells exert their key immunoregulatory functions are largely unknown. Here we found that T cells induced a distinct suppressive state in T cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by T cells was durable and persisted even in the absence of T cells. This durable suppression was due in part to epigenetic changes. The cytokine IL-21 was able to overcome T cell-mediated suppression and inhibited T cells and stimulated B cells. By determining mechanisms of T cell-mediated suppression, we have identified methods for modulating the function of T cells and antibody production.
滤泡调节性T细胞（Tfr细胞）抑制滤泡辅助性T细胞（Tfh细胞）介导的抗体产生。Tfr细胞发挥其关键免疫调节功能的机制在很大程度上尚不清楚。在这里，我们发现Tfr细胞在Tfh细胞和B细胞中诱导了一种独特的抑制状态，其中效应器转录特征得以维持，但关键效应分子和代谢途径受到抑制。Tfr细胞对B细胞抗体产生和代谢的抑制是持久的，即使在没有Tfr细胞的情况下也会持续存在。这种持久的抑制部分归因于表观遗传变化。细胞因子IL-21能够克服Tfr细胞介导的抑制作用，并抑制Tfr细胞并刺激B细胞。通过确定Tfr细胞介导的抑制机制，我们已经确定了调节Tfr细胞功能和抗体产生的方法。
