Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites.
Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites.
复制标题
DOI：
10.1016/j.celrep.2017.08.078
复制
发表时间：
2017-09-19
期刊：
影响因子：
8.8
通讯作者：
Farber DL
中科院分区：
文献类型：
--
作者：
Kumar BV;Ma W;Miron M;Granot T;Guyer RS;Carpenter DJ;Senda T;Sun X;Ho SH;Lerner H;Friedman AL;Shen Y;Farber DL
组织驻留记忆T细胞（TRM）在小鼠中介导对感染和疫苗接种的最佳保护性免疫，而在人类中，TRM的存在和性质尚不清楚。在这里，我们使用一种独特的人体组织资源来确定人体组织记忆T细胞是否在不同的粘膜和淋巴组织中包含一个独特的亚群。我们在肺和脾脏的记忆CD4+和CD8+T细胞的CD69+亚群中发现了一个核心转录谱，与组织和循环中的CD69−TEM细胞不同，并根据与小鼠CD8+TRM转录谱的同源性定义了人类TRM。与循环TEM相比，不同部位的人TRM表现出粘附和抑制分子的表达增加，产生促炎和调节细胞因子，并且增殖减少，表明对原位免疫的独特适应。总之，我们的结果为人类TRM提供了一个统一的特征，并为设计组织靶向免疫疗法提供了蓝图。Kumar等人发现了一个核心的转录和表型特征，该特征定义了CD4+和CD8+ T细胞的人类TRM，该特征在不同的个体以及粘膜和淋巴组织中保存。
Tissue-resident memory T cells (TRM) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRM remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells comprise a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69−TEM cells in tissues and circulation, and defines human TRM based on homology to the transcriptional profile of mouse CD8+TRM. Human TRM in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced proliferation compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies. Kumar et al. identify a core transcriptional and phenotypic signature which defines human TRM for both CD4+ and CD8+ T cells that is preserved across diverse individuals and in mucosal and lymphoid sites.
登录
查看更多内容
影响因子：
30.5
作者：
Schenkel, Jason M.;Fraser, Kathryn A.;Vezys, Vaiva;Masopust, David
通讯作者：
Masopust, David
影响因子：
32.4
作者：
Sathaliyawala T;Kubota M;Yudanin N;Turner D;Camp P;Thome JJ;Bickham KL;Lerner H;Goldstein M;Sykes M;Kato T;Farber DL
通讯作者：
Farber DL
影响因子：
4.4
作者：
Masopust, D;Vezys, V;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
5.8
作者：
Kared, Hassen;Martelli, Serena;Larbi, Anis
通讯作者：
Larbi, Anis
影响因子：
64.8
作者：
Jiang, Xiaodong;Clark, Rachael A.;Liu, Luzheng;Wagers, Amy J.;Fuhlbrigge, Robert C.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.