T Cell Receptor Is Required for Differentiation, but Not Maintenance, of Intestinal CD4(+) Intraepithelial Lymphocytes.
T Cell Receptor Is Required for Differentiation, but Not Maintenance, of Intestinal CD4(+) Intraepithelial Lymphocytes.
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DOI：
10.1016/j.immuni.2020.09.003
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发表时间：
2020-11-17
期刊：
影响因子：
32.4
通讯作者：
Mucida D
中科院分区：
文献类型：
--
作者：
Bilate AM;London M;Castro TBR;Mesin L;Bortolatto J;Kongthong S;Harnagel A;Victora GD;Mucida D
肠上皮细胞由上皮内淋巴细胞（IEL）组成，IEL是一种具有细胞毒性和调节特性的异质性T细胞群，可在上皮层获得。然而，T细胞受体（TCR）在这一过程中的作用仍不清楚。单细胞转录组学分析显示细胞状态之间存在不同的克隆扩增，其中CD4+CD8αα+ IEL是最不多样化的群体之一。条件性缺失分化中的CD4+ T细胞上的TCR或肠上皮细胞上的MHCII阻止了CD4+CD8αα+ IEL的分化。然而，分化的CD4+CD8αα+ IEL上的TCR消融或长期同源抗原撤回并不影响其维持。单核细胞增生李斯特菌对抗原特异性CD4+CD8αα+ IEL的TCR重新接合并未改变其状态，但与细菌侵袭减少相关。因此，局部抗原识别是上皮中CD4+ T细胞分化的必要信号，而分化的IEL能够在不存在TCR信号传导的情况下保留效应程序。免疫细胞对恶劣肠道环境的适应是维持健康肠道的关键。Bilate等人表明，上皮内淋巴细胞的亚群是克隆扩增的，并依赖于抗原受体信号传导进行分化。一旦分化，这些细胞可以在没有抗原的情况下茁壮成长，突出了这些细胞在不同环境下维持功能的能力。
The gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneous T cell population with cytotoxic and regulatory properties, which can be acquired at the epithelial layer. However, the role of T cell receptor (TCR) in this process remains unclear. Single-cell transcriptomic analyses revealed distinct clonal expansions between cell states, with CD4+CD8αα+ IELs being one of the least diverse populations. Conditional deletion of TCR on differentiating CD4+ T cells or of MHCII on intestinal epithelial cells prevented CD4+CD8αα+ IEL differentiation. However, TCR ablation on differentiated CD4+CD8αα+ IELs, or long-term cognate antigen withdraw, did not affect their maintenance. TCR re-engagement of antigen-specific CD4+CD8αα+ IELs by Listeria monocytogenes did not alter their state but correlated with reduced bacterial invasion. Thus, local antigen recognition is an essential signal for differentiation of CD4+ T cells at the epithelium yet differentiated IELs are able to preserve an effector program in the absence of TCR signaling. Immune cell adaptation to the harsh intestinal environment is key for healthy gut maintenance. Bilate et al. showed that a subpopulation of intraepithelial lymphocytes is clonally expanded and depends on antigen receptor signaling for their differentiation. Once differentiated, these cells can thrive without antigen, highlighting the ability of these cells to maintain function under different contexts.
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影响因子：
46.9
作者：
Han, Arnold;Glanville, Jacob;Hansmann, Leo;Davis, Mark M.
通讯作者：
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DOI：
10.1084/jem.173.2.471
发表时间：
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期刊：
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