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Eomes 鉴定了自身特异性记忆表型 CD8 T 细胞的胸腺前体细胞。

Eomes identifies thymic precursors of self-specific memory-phenotype CD8 T cells.

机构信息

Department of Pathology, University of Chicago, Chicago, IL, USA.

Bioinformatics Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

出版信息

Nat Immunol. 2020 May;21(5):567-577. doi: 10.1038/s41590-020-0653-1. Epub 2020 Apr 13.

DOI:10.1038/s41590-020-0653-1
PMID:32284593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7193531/
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.

摘要

未成熟的小鼠体内存在大量具有“记忆表型”的 CD8 T 细胞（CD8-MP 细胞），这些细胞表现出激活和先天样功能特性的特征。由于缺乏可靠的标志物来区分 CD8-MP 细胞与真正的 CD8 记忆 T 细胞，CD8-MP 细胞的发育起源和抗原特异性仍不完全确定。通过深度 T 细胞抗原受体（TCR）测序，我们发现 CD8-MP 细胞表达的 TCR 高度重复，与幼稚表型 CD8 T 细胞表达的 TCR 不同。CD8-MP 克隆对广泛表达的自身配体表现出反应性。在胸腺中成熟过程中，表达 CD8-MP TCR 的 T 细胞前体就会上调转录因子 Eomes 的表达，而无需诱导完全的记忆表型，这表明在识别自身配体后会触发一个独特的程序。此外，CD8-MP 细胞浸润致癌基因驱动的前列腺肿瘤，并表达高水平的 PD-1，这表明它们在抗肿瘤免疫和免疫治疗反应中可能发挥作用。

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