Lineage Tracking the Generation of T Regulatory Cells From Microbial Activated T Effector Cells in Naïve Mice

Frontiers in Immunology

Mingjuan Qu¹  Chenfeng He²  Qijing Li³  Si-Qi Liu³  Xiaobo Zhou⁴  Lin Shi⁴  Yae Sun⁴  Baojun Zhang⁴  Tao Xie⁴  Yanbin Cheng⁴  Dan Zhang⁴  Kun Zhu⁴  Lei Lei⁴  Xiaofeng Yang⁴  Huiqiang Zheng⁴  Xiaonan Shen⁴  Ning Jiang⁵ 

[1] College of Life Sciences, Ludong University, Yantai, China;Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States;Department of Immunology, Duke University Medical Center, Durham, NC, United States;Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China;Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, United States;

关键词: tolerance;    inducible Tregs;    microbiota;    gut;    TCR repertoire;   

DOI  :  10.3389/fimmu.2019.03109

来源: DOAJ

【 摘 要 】

Regulatory T cells (Tregs) are essential for the maintenance of gut homeostasis by suppressing conventional CD4+ helper T cells (Tconvs) that are activated by microbial antigens. Although thymus is the major source of the peripheral Tregs, peripheral conversion from Tconvs to Tregs have also been shown to occur under various experimental conditions. It remains less clear about the frequency of lineage conversion from Tconvs to Tregs in naïve animals. Here we used a newly established reporter system to track a group of post expansion Tregs (eTregs), which exhibited a stronger suppressive ability than the non-lineage marked Tregs. Notably, microbial antigens are the primary driver for the formation of eTregs. TCR repertoire analysis of Peyer's patch T cells revealed that eTregs are clonally related to Tconvs, but not to the non-lineage tracked Tregs. Adoptive transfer of Tconvs into lymphopenic hosts demonstrated a conversion from Tconvs to eTregs. Thus, our lineage tracking method was able to capture the lineage conversion from microbial activated effector T cells to Tregs in naïve animals. This study suggests that a fraction of clonally activated T cells from the natural T cell repertoire exhibits lineage conversion to Tregs in response to commensal microbes under homeostatic conditions.

【 授权许可】

Unknown