Yi Jaeu, Jung Jisun, Han Daehee, Surh Charles D, Lee You Jeong
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37673, Korea.
Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37673, Korea.
Mol Cells. 2019 Mar 31;42(3):228-236. doi: 10.14348/molcells.2018.0424. Epub 2019 Feb 8.
CD4 T cells differentiate into RORγt/IL-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.
在被分节丝状菌（SFB）定殖后，CD4 T细胞在小肠中分化为表达RORγt/IL-17A的细胞。然而，尚不清楚SFB特异性CD4 T细胞是否能直接从初始前体分化而来，以及它们的效应分化是否仅指向Th17谱系。在本研究中，我们通过过继性T细胞转移实验表明，初始CD4 T细胞可迁移至小肠固有层（sLP）并分化为效应T细胞，这些效应T细胞在SFB定殖后合成IL-17A。通过单细胞RT-PCR分析，我们表明对SFB作出反应的T细胞后代并不均一，而是由转录上不同的群体组成，包括Th1、Th17和滤泡辅助性T细胞。我们在同源抗原存在的情况下培养SFB特异性肠道CD4 T细胞，进一步证实了这一发现，其也产生了具有相似特征的异质群体。总的来说，这些发现表明单一物种的肠道细菌可产生不同的抗原特异性效应CD4 T细胞群体，而不是为特定效应T细胞亚群的发育提供细胞因子环境。
