生物
细胞毒性T细胞
CD8型
免疫学
T细胞
免疫系统
白细胞介素21
背景(考古学)
效应器
细胞生物学
白细胞介素2受体
遗传学
体外
古生物学
作者
Takuya Sekine,André Perez-Potti,SonBinh T. Nguyen,Jean-Baptiste Gorin,Vin-Cent Wu,Emma Gostick,Sian Llewellyn-Lacey,Quirin Hammer,Sara Falck-Jones,Sindhu Vangeti,Meng Yu,Anna Smed-Sörensen,Ahmed Gaballa,Michael Uhlin,Johan K. Sandberg,Christian Brander,Piotr Nowak,Paul A. Goepfert,David Price,Michael R. Betts,Marcus Buggert
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2020-07-03
卷期号:5 (49)
被引量:87
标识
DOI:10.1126/sciimmunol.aba7918
摘要
CD8+ T cell exhaustion is a hallmark of many cancers and chronic infections. In mice, T cell factor 1 (TCF-1) maintains exhausted CD8+ T cell responses, whereas thymocyte selection-associated HMG box (TOX) is required for the epigenetic remodeling and survival of exhausted CD8+ T cells. However, it has remained unclear to what extent these transcription factors play analogous roles in humans. In this study, we mapped the expression of TOX and TCF-1 as a function of differentiation and specificity in the human CD8+ T cell landscape. Here, we demonstrate that circulating TOX+ CD8+ T cells exist in most humans, but that TOX is not exclusively associated with exhaustion. Effector memory CD8+ T cells generally expressed TOX, whereas naive and early-differentiated memory CD8+ T cells generally expressed TCF-1. Cytolytic gene and protein expression signatures were also defined by the expression of TOX. In the context of a relentless immune challenge, exhausted HIV-specific CD8+ T cells commonly expressed TOX, often in clusters with various activation markers and inhibitory receptors, and expressed less TCF-1. However, polyfunctional memory CD8+ T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) also expressed TOX, either with or without TCF-1. A similar phenotype was observed among HIV-specific CD8+ T cells from individuals who maintained exceptional immune control of viral replication. Collectively, these data demonstrate that TOX is expressed by most circulating effector memory CD8+ T cell subsets and not exclusively linked to exhaustion.
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