Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Bioinformatics Core Facility, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Nat Commun. 2017 Nov 13;8(1):1473. doi: 10.1038/s41467-017-01728-5.
The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56 TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56 TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.
CD45RA 的表达通常与幼稚 T 细胞有关。然而，在抗原刺激后，效应记忆 T 细胞的亚群会重新表达 CD45RA（称为 TEMRA），但其分子特征和功能尚不清楚。CD4 TEMRA 细胞已被证明与登革热病毒（DENV）等病原体的保护性免疫有关。在这里，我们表明，不仅 CD4 TEMRA 细胞的频率，而且其表型在个体之间也是异质的。这些细胞可以根据粘附 G 蛋白偶联受体 GPR56 的表达进一步分为两个主要亚群，GPR56 TEMRA 细胞显示出具有细胞毒性特征的转录和蛋白质组程序，与效应记忆 T 细胞不同。此外，GPR56 TEMRA 细胞具有更高水平的克隆扩增，并包含大多数病毒特异性 TEMRA 细胞。总的来说，这项研究揭示了 CD4 TEMRA 细胞的异质性，并为针对 DENV 和其他病毒病原体的 T 细胞反应提供了新的见解。
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