Eomes是自特異性記憶表型CD8+T細胞的前體細胞標誌

Eomes是自特異性記憶表型CD8+T細胞的前體細胞標誌

作者：

小柯機器人

發布時間：2020/4/19 23:12:46

美國芝加哥大學Peter A. Savage研究團隊的一項最新表明，Eomes是自特異性記憶表型CD8⁺T細胞的胸腺前體細胞標誌。相關論文於2020年4月13日在線發表在《自然—免疫學》雜誌上。

研究人員表示，未活化的小鼠具有大量的「記憶表型」 CD8⁺T細胞（CD8-MP細胞），這些細胞表現出激活的特徵和類似先天的功能特性。由於缺乏可靠的標記來區分CD8-MP細胞和真正的CD8⁺記憶T細胞，因此CD8-MP細胞的發育起源和抗原特異性仍未完全確定。

 

通過使用深度T細胞抗原受體（TCR）測序，研究人員發現CD8-MP細胞表達的TCR高度重複，並且不同於初始表型CD8⁺T細胞表達的TCR。CD8-MP克隆表現出對廣泛表達的自身配體的反應性。

 

在誘導全記憶表型之前，表達CD8-MP TCR的T細胞前體在胸腺成熟過程中顯示出轉錄因子Eomes的上調，這暗示著識別自配體會觸發一個獨特的程序。

 

此外，CD8-MP細胞浸潤癌基因驅動的前列腺腫瘤並表達高密度的PD-1，這提示其在抗腫瘤免疫和免疫治療應答中具有潛在作用。

 

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