Ritvo Paul-Gydeon G, Churlaud Guillame, Quiniou Valentin, Florez Laura, Brimaud Faustine, Fourcade Gwladys, Mariotti-Ferrandiz Encarnita, Klatzmann David
Sorbonne Université, University Pierre and Marie Curie (UPMC), Univ Paris 06, INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (i3), F-75005 Paris, France.
AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi), and Inflammation-Immunopathology-Biotherapy Department (i2B), F-75651 Paris, France.
Sci Immunol. 2017 Sep 8;2(15). doi: 10.1126/sciimmunol.aan0368.
Follicular regulatory T (T) cells from lymph node germinal centers control follicular helper T (T) cell-dependent B cell activation. These scarce cells, often described and purified as CD25 cells, are thought to be derived from thymic regulatory T (T) cells. However, we observed that mouse T cells do not respond to interleukin-2 (IL-2), unlike T cells. Stringent immunophenotyping based on B cell lymphoma 6 (Bcl6), programmed cell death protein 1 (PD-1), and CXCR5 expression revealed that T cells are actually CD25, in mice and humans. Moreover, T cell characterization based only on CXCR5 and PD-1 high expression without excluding CD25 cells resulted in contamination with T cells. Transcriptome studies of CD4CXCR5PD-1Bcl6Foxp3CD25 T cells revealed that they express the IL-1 decoy receptor IL-1R2 and the IL-1 receptor antagonist IL-1Ra, whereas T cells express the IL-1R1 agonist receptor. IL-1 treatment expanded T cells in vivo and activated their production of IL-4 and IL-21 in vitro. T cells suppressed the IL-1-induced activation of T cells as efficiently as the IL-1 receptor antagonist Anakinra. Altogether, these results reveal an IL-1 axis in the T cell control of B cell responses and an IL-2/IL-1 dichotomy for T cell control of effector T cells versus T cell control of T cells.
来自淋巴结生发中心的滤泡调节性T（Treg）细胞控制滤泡辅助性T（Tfh）细胞依赖性B细胞活化。这些稀少的细胞，通常被描述和纯化为CD25⁺细胞，被认为来源于胸腺调节性T细胞。然而，我们观察到小鼠Treg细胞与T细胞不同，对白细胞介素-2（IL-2）无反应。基于B细胞淋巴瘤6（Bcl6）、程序性细胞死亡蛋白1（PD-1）和CXCR5表达的严格免疫表型分析表明，在小鼠和人类中，Treg细胞实际上是CD25⁻。此外，仅基于CXCR5和PD-1高表达而不排除CD25⁺细胞的Tfh细胞表征会导致Treg细胞污染。对CD4⁺CXCR5⁺PD-1⁺Bcl6⁺Foxp3⁺CD25⁻ Tfh细胞的转录组研究表明，它们表达IL-1诱饵受体IL-1R2和IL-1受体拮抗剂IL-1Ra，而Treg细胞表达IL-1R1激动剂受体。IL-1处理在体内扩增了Tfh细胞，并在体外激活了它们的IL-4和IL-21产生。Tfh细胞抑制IL-1诱导的Treg细胞活化的效率与IL-1受体拮抗剂阿那白滞素相同。总之，这些结果揭示了Tfh细胞控制B细胞反应中的IL-1轴，以及Treg细胞控制效应T细胞与Tfh细胞控制Treg细胞的IL-2/IL-1二分法。
