Department of Internal Medicine II, Division of Hematology, Universitätsklinikum Würzburg, Würzburg, Germany.
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Immunol Cell Biol. 2014 Sep;92(8):659-70. doi: 10.1038/icb.2014.34. Epub 2014 May 13.
Unlike induced Foxp3(+) regulatory T cells (Foxp3(+) iTreg) that have been shown to play an essential role in the development of protective immunity to the ubiquitous mold Aspergillus fumigatus, type-(1)-regulatory T cells (Tr1) cells have, thus far, not been implicated in this process. Here, we evaluated the role of Tr1 cells specific for an epitope derived from the cell wall glucanase Crf-1 of A. fumigatus (Crf-1/p41) in antifungal immunity. We identified Crf-1/p41-specific latent-associated peptide(+) Tr1 cells in healthy humans and mice after vaccination with Crf-1/p41+zymosan. These cells produced high amounts of interleukin (IL)-10 and suppressed the expansion of antigen-specific T cells in vitro and in vivo. In mice, in vivo differentiation of Tr1 cells was dependent on the presence of the aryl hydrocarbon receptor, c-Maf and IL-27. Moreover, in comparison to Tr1 cells, Foxp3(+) iTreg that recognize the same epitope were induced in an interferon gamma-type inflammatory environment and more potently suppressed innate immune cell activities. Overall, our data show that Tr1 cells are involved in the maintenance of antifungal immune homeostasis, and most likely play a distinct, yet complementary, role compared with Foxp3(+) iTreg.
与已被证明在对抗普遍存在的曲霉菌（Aspergillus fumigatus）的保护性免疫中发挥重要作用的诱导 Foxp3(+)调节性 T 细胞（Foxp3(+)iTreg）不同，迄今为止，1 型调节性 T 细胞（Tr1）尚未被牵连到这一过程中。在这里，我们评估了针对曲霉菌细胞壁葡聚糖酶 Crf-1 的表位（Crf-1/p41）的 Tr1 细胞在抗真菌免疫中的作用。我们在接种 Crf-1/p41+酵母聚糖后，在健康人类和小鼠中鉴定出了 Crf-1/p41 特异性潜伏相关肽（+）Tr1 细胞。这些细胞产生大量白细胞介素（IL）-10，并在体外和体内抑制抗原特异性 T 细胞的扩增。在小鼠中，Tr1 细胞的体内分化依赖于芳香烃受体、c-Maf 和 IL-27 的存在。此外，与 Tr1 细胞相比，识别相同表位的 Foxp3(+)iTreg 在干扰素γ型炎症环境中被诱导，并更有效地抑制固有免疫细胞的活性。总的来说，我们的数据表明 Tr1 细胞参与维持抗真菌免疫的稳态，并且与 Foxp3(+)iTreg 相比，很可能发挥独特但互补的作用。
