美国麻省大学医学院Eric S. Huseby团队研究出胸腺在时间上的选择转换和配体结合动力学限制了新生Foxp3⁺T细胞的发育。 2019年8月出版的《自然—免疫学》发表了这项成果。

研究小组确定被新生儿tT_reg细胞识别的17条自身多肽，揭示了包含自体抗原以年龄和炎症依赖方式呈现的配体特异性模式,。对新生儿肽基精氨酸脱氨酶 IV型(Padi4)特异胸腺细胞的命运映射研究，揭示了不同的命运选择。新生儿胸腺细胞表达的T细胞受体使得IAb-Padi4在传统的对接方向停留中等时间，该受体像tTreg细胞一样被导出。相比之下，停顿时间较短的Padi4-特异T细胞受体表达在CD4⁺ T细胞，停留长时间的诱导负向选择。Padi4特异性胸腺细胞短暂地在负向选择中经历发一个育阶段特异性改变，这阻碍了tT_reg细胞的发育。因此，负向选择的时间转换和配体结合动力学，限制了新生儿tT_reg的选择窗口。

据悉，新生儿胸腺产生Foxp3⁺调节性T（tT_reg）细胞，这些细胞在控制免疫自稳和预防多器官自身免疫方面起关键作用。抗原特异性在新生儿tT_reg细胞筛选上所起的作用尚未了解。

附：英文原文

Title: A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3 + T reg cell development

Author: Brian D. Stadinski, Sydney J. Blevins, Nicholas A. Spidale, Brian R. Duke, Priya G. Huseby, Lawrence J. Stern, Eric S. Huseby

Issue&Volume: Volume 20 Issue 8

Abstract: The neonatal thymus generates Foxp3+ regulatory T (tTreg) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tTreg cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tTreg cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IAb-Padi4 with moderate dwell times within a conventional docking orientation are exported as tTreg cells. In contrast, Padi4-specific T cell receptors with short dwell times are expressed on CD4+ T cells, while long dwell times induce negative selection. Temporally, Padi4-specific thymocytes are subject to a developmental stage-specific change in negative selection, which precludes tTreg cell development. Thus, a temporal switch in negative selection and ligand binding kinetics constrains the neonatal tTreg selection window.

DOI: 10.1038/s41590-019-0414-1

Source:https://www.nature.com/articles/s41590-019-0414-1