ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells
ABC transporters and NR4A1 identify a quiescent subset of tissue-resident memory T cells
复制标题
ABC转运蛋白和NR4A1识别组织驻留记忆T细胞的静止亚群
DOI：
10.1172/jci85329
复制
发表时间：
2016-10-01
影响因子：
15.9
通讯作者：
Dhodapkar, Madhav V.
中科院分区：
文献类型：
--
作者：
Boddupalli, Chandra Sekhar;Nair, Shiny;Dhodapkar, Madhav V.
组织中的免疫监视由组织驻留记忆T细胞（Trm细胞）的长寿命亚群介导。一个假定的组织驻留的长寿干细胞的子集的特征在于外排Hoechst染料的能力，并被称为侧群（SP）细胞。在这里，我们已经表征了在人类和小鼠中表现出静止（G（0））表型的SP T细胞（Tsp细胞）的子集。肠道和BM中的人Trm细胞富集于主要处于细胞周期G（0）期的Tsp细胞中。此外，在组蛋白2B-GFP小鼠中，2B-GFP标记保留在Tsp细胞中，指示慢循环表型。人Tsp细胞显示出独特的基因表达谱，其富集了在Trm细胞中过表达的基因。在小鼠中，由Tsp标签基因编码的蛋白质，包括核受体亚家族4 A组成员1（NR 4A 1）和ATP结合盒（ABC）转运蛋白，影响Trm细胞的功能和分化。对人Tsp细胞过继转移至免疫缺陷小鼠和普乐沙福治疗的反应表明，人Tsp细胞动员可作为一种潜在的细胞治疗。这些数据鉴定了具有静止/慢循环表型、组织富集倾向和动员到循环中的潜力的人T细胞的不同子集，其可用于过继性细胞治疗。
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G(0)) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G(0) stage of the cell cycle. Moreover, in histone 2B-GFP mice, the 2B-GFP label was retained in Tsp cells, indicative of a slow-cycling phenotype. Human Tsp cells displayed a distinct gene-expression profile that was enriched for genes overexpressed in Trm cells. In mice, proteins encoded by Tsp signature genes, including nuclear receptor subfamily 4 group A member 1 (NR4A1) and ATP-binding cassette (ABC) transporters, influenced the function and differentiation of Trm cells. Responses to adoptive transfer of human Tsp cells into immune-deficient mice and plerixafor therapy suggested that human Tsp cell mobilization could be manipulated as a potential cellular therapy. These data identify a distinct subset of human T cells with a quiescent/slow-cycling phenotype, propensity for tissue enrichment, and potential to mobilize into circulation, which may be harnessed for adoptive cellular therapy.