小柯机器人

Eomes是自特异性记忆表型CD8+T细胞的前体细胞标志
2020-04-19 23:12

美国芝加哥大学Peter A. Savage研究团队的一项最新表明,Eomes是自特异性记忆表型CD8+T细胞的胸腺前体细胞标志。相关论文于2020年4月13日在线发表在《自然—免疫学》杂志上。

研究人员表示,未活化的小鼠具有大量的“记忆表型” CD8+T细胞(CD8-MP细胞),这些细胞表现出激活的特征和类似先天的功能特性。由于缺乏可靠的标记来区分CD8-MP细胞和真正的CD8+记忆T细胞,因此CD8-MP细胞的发育起源和抗原特异性仍未完全确定。
 
通过使用深度T细胞抗原受体(TCR)测序,研究人员发现CD8-MP细胞表达的TCR高度重复,并且不同于初始表型CD8+T细胞表达的TCR。CD8-MP克隆表现出对广泛表达的自身配体的反应性。
 
在诱导全记忆表型之前,表达CD8-MP TCR的T细胞前体在胸腺成熟过程中显示出转录因子Eomes的上调,这暗示着识别自配体会触发一个独特的程序。
 
此外,CD8-MP细胞浸润癌基因驱动的前列腺肿瘤并表达高密度的PD-1,这提示其在抗肿瘤免疫和免疫治疗应答中具有潜在作用。
 
附:英文原文

Title: Eomes identifies thymic precursors of self-specific memory-phenotype CD8 + T cells

Author: Christine H. Miller, David E. J. Klawon, Sharon Zeng, Victoria Lee, Nicholas D. Socci, Peter A. Savage

Issue&Volume: 2020-04-13

Abstract: Unprimed mice harbor a substantial population of ‘memory-phenotype’ CD8+ T cells (CD8-MP cells) that exhibit hallmarks of activation and innate-like functional properties. Due to the lack of faithful markers to distinguish CD8-MP cells from bona fide CD8+ memory T cells, the developmental origins and antigen specificities of CD8-MP cells remain incompletely defined. Using deep T cell antigen receptor (TCR) sequencing, we found that the TCRs expressed by CD8-MP cells are highly recurrent and distinct from the TCRs expressed by naive-phenotype CD8+ T cells. CD8-MP clones exhibited reactivity to widely expressed self-ligands. T cell precursors expressing CD8-MP TCRs showed upregulation of the transcription factor Eomes during maturation in the thymus, prior to induction of the full memory phenotype, which is suggestive of a unique program triggered by recognition of self-ligands. Moreover, CD8-MP cells infiltrate oncogene-driven prostate tumors and express high densities of PD-1, which suggests potential roles in antitumor immunity and the response to immunotherapy.

DOI: 10.1038/s41590-020-0653-1

Source: https://www.nature.com/articles/s41590-020-0653-1

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

分享到:

0