CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.
CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.
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DOI：
10.1038/mi.2015.69
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发表时间：
2016-03
影响因子：
8
通讯作者：
Klenerman P
中科院分区：
文献类型：
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作者：
Fergusson JR;Hühn MH;Swadling L;Walker LJ;Kurioka A;Llibre A;Bertoletti A;Holländer G;Newell EW;Davis MM;Sverremark-Ekström E;Powrie F;Capone S;Folgori A;Barnes E;Willberg CB;Ussher JE;Klenerman P
C型凝集素样受体CD 161在人类肠道和肝脏以及血液中发现的淋巴细胞上表达，特别是自然杀伤细胞，T辅助细胞17和称为粘液相关恒定T（MAIT）细胞的非常规T细胞群。建立了高CD 161表达与包括MAIT细胞在内的先天性T细胞群的关联。在这里，我们表明，CD 161也表达，在中等水平，在一个突出的亚群的多克隆CD 8 + T细胞，包括抗病毒群体，显示记忆表型。这些记忆性CD 161 int CD 8 + T细胞在结肠内富集，并表达与组织驻留相关的标志物CD 103和CD 69。此外，该人群的特征在于增强的多功能性，细胞毒性介质的水平增加和转录因子T-bet和Eomesodermin的高表达。这些人群是由基于腺病毒载体的新疫苗策略诱导的，目前正在试验中对抗丙型肝炎病毒。因此，中等水平的CD 161表达标志着人类中有效的多克隆、多功能组织归巢CD 8 + T细胞群。由于诱导这种反应代表了T细胞预防性和治疗性疫苗在病毒性疾病和癌症中的主要目的，因此对这些群体的分析在未来可能具有价值。
The C-type lectin-like receptor CD161 is expressed on lymphocytes found in human gut and liver, as well as blood, especially Natural Killer cells, T helper 17 cells and a population of unconventional T cells known as Mucosal Associated Invariant T (MAIT) cells. The association of high CD161 expression with innate T cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including anti-viral populations, which display a memory phenotype. These memory CD161int CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterised by enhanced polyfunctionality, increased levels of cytotoxic mediators and high expression of the transcription factors T-bet and Eomesodermin. Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against Hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T cell populations in humans. Since induction of such responses represents a major aim of T cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.