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Differential control of immune cell homeostasis by Foxp3+regulatory T cells in murine peripheral lymph nodes and spleen

机译:Foxp3 +对免疫细胞稳态的差异控制鼠外周淋巴结和脾脏中的调节性T细胞

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摘要

Foxp3+ regulatory T cells (Tregs) hamper efficient immune responses to tumors and chronic infections. Therefore, depletion of Foxp3+ Tregs has been proposed as therapeutic option to boost immune responses and to improve vaccinations. Although Treg-mediated control of T cell homeostasis is well established, Foxp3+ Treg interaction with other immune cell subsets is only incompletely understood. Thus, the present study aimed at examining dynamic effects of experimental Foxp3+ Treg depletion on a broad range of immune cell subsets, including B cells, natural killer cells, and myeloid cells. Striking differences were observed when peripheral lymph nodes (LN) and spleen were compared. B cells, for example, showed a massive and long-lasting accumulation only in LN but not in spleen of transiently Treg-depleted mice. In contrast, monocyte-derived dendritic cells, which are potent inducers of T cell responses, also accumulated selectively, but only transiently in LN, suggesting that this cell population is under very strict control of Foxp3+ Tregs. In summary, the observations described here provide insights into the dynamics of immune cells after selective depletion of Foxp3+ Tregs. This will allow a better prediction of the impactof Treg ablation in translational studies that aim at boosting immune responsesand vaccinations.
机译:Foxp3 + 调节性T细胞(Tregs)阻碍了对肿瘤和慢性感染的有效免疫反应。因此,Foxp3 + Tregs的消耗被提出作为增强免疫反应和改善疫苗接种的治疗选择。尽管已经很好地确定了Treg介导的T细胞稳态控制,但是对Foxp3 + Treg与其他免疫细胞亚群的相互作用的了解还不完全。因此,本研究旨在研究实验性Foxp3 + Treg耗竭对广泛免疫细胞亚群(包括B细胞,自然杀伤细胞和髓样细胞)的动态影响。比较外周淋巴结(LN)和脾脏时,观察到惊人的差异。例如,B细胞仅在LN短暂缺乏Treg的小鼠的脾脏中显示大量且持久的蓄积。相比之下,单核细胞衍生的树突状细胞是T细胞反应的强效诱导剂,也选择性地积累,但仅在LN中短暂地积累,这表明该细胞群受到Foxp3 + Tregs的严格控制。总之,本文描述的观察结果提供了对Foxp3 + Treg选择性消耗后免疫细胞动力学的见解。这样可以更好地预测影响Treg切除在旨在促进免疫反应的转化研究中的应用和疫苗接种。

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