The medulla controls effector primed ?dT-cell development in the adult mouse thymus.
The medulla controls effector primed ?dT-cell development in the adult mouse thymus.
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髓质控制成年小鼠胸腺中效应器引发的 dT 细胞的发育。
DOI：
10.1002/eji.202350388
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发表时间：
2023
影响因子：
5.4
通讯作者：
James KD
中科院分区：
文献类型：
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作者：
James KD
γδT细胞在整个生命过程中在胸腺中产生，并在富含上皮的部位提供免疫力。与传统的αβT细胞不同，γδT细胞的发育涉及胸腺内获得效应子功能，分别在胚胎或成年期引发IL 17或IFN-γ的产生。人们对胸腺如何控制成年期效应子引发的γδT细胞的产生知之甚少。在这里，我们使用Rag 2GFP小鼠以及成熟/效应物引发的标志物（包括CD 24、CD 25、CD 73和IFN-γ）将从头γδT细胞与经历胸腺再循环和/或保留的那些细胞区分开来，后者通过与IFN-γYFPGREAT小鼠杂交。我们将新发育的γδT细胞分类为有序序列，其中CD 25 + CD 73 −IFN-γYFP−前体依次为CD 25 − CD 73 +IFN-γYFP−中间体和CD 25 − CD 73 +IFN-γYFP+效应子。为了确定控制这一序列的胸腺内需求，我们检查了缺乏髓质微环境的Relb −/−胸腺移植物中γδT细胞的发育。有趣的是，髓质缺陷并没有改变CD 25 +γδT细胞前体的产生，但显著损害了效应启动阶段的发育。这种对γδT细胞启动的影响在缺乏髓样趋化因子CCL 19和CCL 21的plt/plt小鼠以及Ccl 21 a −/−但不是Ccl 19 −/−小鼠中得到反映。总的来说，我们确定了髓质作为成人γδT细胞发育过程中效应启动的重要部位，并证明了髓质上皮产物CCL 21在此过程中的特定作用。
γδT cells are produced in the thymus throughout life and provide immunity at epithelial‐rich sites. Unlike conventional αβT cells, γδT‐cell development involves intrathymic acquisition of effector function, with priming for either IL17 or IFN‐γ production occurring during embryonic or adult life, respectively. How the thymus controls effector‐primed γδT‐cell generation in adulthood is poorly understood. Here, we distinguished de novo γδT cells from those undergoing thymus recirculation and/or retention using Rag2GFP mice alongside markers of maturation/effector priming including CD24, CD25, CD73, and IFN‐γ, the latter by crossing with IFN‐γYFPGREAT mice. We categorize newly developing γδT‐cells into an ordered sequence where CD25+CD73−IFN‐γYFP−precursors are followed sequentially by CD25−CD73+IFN‐γYFP−intermediates and CD25−CD73+IFN‐γYFP+effectors. To determine intrathymic requirements controlling this sequence, we examined γδT‐cell development inRelb−/−thymus grafts that lack medullary microenvironments. Interestingly, medulla deficiency did not alter CD25+γδT‐cell precursor generation, but significantly impaired development of effector primed stages. This impact on γδT‐cell priming was mirrored inplt/pltmice lacking the medullary chemoattractants CCL19 and CCL21, and alsoCcl21a−/−but notCcl19−/−mice. Collectively, we identify the medulla as an important site for effector priming during adult γδT‐cell development and demonstrate a specific role for the medullary epithelial product CCL21 in this process.