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T细胞受体是肠道CD4+上皮内淋巴细胞分化而非维持所必需
作者:小柯机器人 发布时间:2020/10/11 21:40:10

美国洛克菲勒大学Daniel Mucida、Angelina M. Bilate等研究人员合作发现,T细胞受体是肠道CD4+上皮内淋巴细胞分化而非维持所必需。这一研究成果于2020年10月5日在线发表在国际学术期刊《免疫》上。

研究人员表示,肠上皮细胞由上皮内淋巴细胞(IEL)组成,上皮内淋巴细胞是具有细胞毒性和调节特性的异种T细胞群体,可以在上皮层获得。但是,在这一过程中T细胞受体(TCR)的作用仍不清楚。
 
通过单细胞转录组学分析,研究人员揭示了细胞状态之间明显的克隆扩增,其中CD4+CD8αα+IEL是分布最少的群体之一。条件性敲除分化的CD4+T细胞上的TCR或肠上皮细胞上的MHCII可防止CD4+CD8αα+IEL分化。然而,对分化的CD4+CD8αα+IEL进行TCR敲除或长期撤除相关抗原不会影响其维持。
 
单核细胞增生性李斯特菌的抗原特异性CD4+CD8αα+IEL与TCR的重新结合不会改变其状态,但与细菌入侵的减少有关。因此,局部抗原识别是上皮细胞CD4+T细胞分化的重要信号,而分化的IEL可以在没有TCR信号的情况下保留效应子程序。
 
附:英文原文

Title: T Cell Receptor Is Required for Differentiation, but Not Maintenance, of Intestinal CD4+ Intraepithelial Lymphocytes

Author: Angelina M. Bilate, Mariya London, Tiago B.R. Castro, Luka Mesin, Juliana Bortolatto, Suppawat Kongthong, Audrey Harnagel, Gabriel D. Victora, Daniel Mucida

Issue&Volume: 2020-10-05

Abstract: The gut epithelium is populated by intraepithelial lymphocytes (IELs), a heterogeneousT cell population with cytotoxic and regulatory properties, which can be acquiredat the epithelial layer. However, the role of T cell receptor (TCR) in this processremains unclear. Single-cell transcriptomic analyses revealed distinct clonal expansionsbetween cell states, with CD4+CD8αα+ IELs being one of the least diverse populations. Conditional deletion of TCR on differentiatingCD4+ T cells or of major histocompatibility complex (MHC) class II on intestinal epithelialcells prevented CD4+CD8αα+ IEL differentiation. However, TCR ablation on differentiated CD4+CD8αα+ IELs or long-term cognate antigen withdraw did not affect their maintenance. TCRre-engagement of antigen-specific CD4+CD8αα+ IELs by Listeria monocytogenes did not alter their state but correlated with reduced bacterial invasion. Thus, localantigen recognition is an essential signal for differentiation of CD4+ T cells at the epithelium, yet differentiated IELs are able to preserve an effectorprogram in the absence of TCR signaling.

DOI: 10.1016/j.immuni.2020.09.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30397-6

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx