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KLRG1+ Memory CD8 T Cells Combine Properties of Short-Lived Effectors and Long-Lived Memory
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-07-01 , DOI: 10.4049/jimmunol.1901512
Kristin R Renkema 1, 2 , Matthew A Huggins 1, 2 , Henrique Borges da Silva 1, 2 , Todd P Knutson 3 , Christy M Henzler 3 , Sara E Hamilton 2, 4
Affiliation  

Key Points LLEC exhibit transcriptional characteristics common to effector and memory T cells. LLEC undergo homeostatic proliferation but do not critically depend on IL-15. LLEC are predominantly derived from KLRG1hi effector cells at 12 d postinfection. CD8 effector T cells with a CD127hi KLRG1− phenotype are considered precursors to the long-lived memory pool, whereas KLRG1+CD127low cells are viewed as short-lived effectors. Nevertheless, we and others have shown that a KLRG1+CD127low population persists into the memory phase and that these T cells (termed long-lived effector cells [LLEC]) display robust protective function during acute rechallenge with bacteria or viruses. Whether these T cells represent a true memory population or are instead a remnant effector cell population that failed to undergo initial contraction has remained unclear. In this study, we show that LLEC from mice express a distinct phenotypic and transcriptional signature that shares characteristics of both early effectors and long-lived memory cells. We also find that in contrast to KLRG1+ effector cells, LLEC undergo homeostatic proliferation and are not critically dependent on IL-15 for their maintenance. Furthermore, we find that LLEC are predominantly derived from KLRG1+ effector cells when isolated at day 12 of the response. Our work challenges the concept that the KLRG1+CD127low population is dominated by short-lived cells and shows that KLRG1 downregulation is not a prerequisite to become a long-lived protective memory T cell.

中文翻译:

KLRG1+ 记忆 CD8 T 细胞结合了短寿命效应器和长寿命记忆的特性

要点 LLEC 表现出效应 T 细胞和记忆 T 细胞共有的转录特征。LLEC 经历稳态增殖但不严重依赖 IL-15。LLEC 主要来源于感染后 12 天的 KLRG1hi 效应细胞。具有 CD127hi KLRG1− 表型的 CD8 效应 T 细胞被认为是长寿命记忆池的前体,而 KLRG1+CD127low 细胞被视为短寿命效应细胞。尽管如此,我们和其他人已经表明,KLRG1+CD127low 群体持续进入记忆阶段,并且这些 T 细胞(称为长寿命效应细胞 [LLEC])在细菌或病毒的急性再攻击期间显示出强大的保护功能。这些 T 细胞是代表真正的记忆细胞群,还是未能进行初始收缩的残余效应细胞群仍不清楚。在这项研究中,我们表明来自小鼠的 LLEC 表达了一种独特的表型和转录特征,这些特征具有早期效应细胞和长寿记忆细胞的特征。我们还发现,与 KLRG1+ 效应细胞相比,LLEC 会进行稳态增殖,并且不会严重依赖 IL-15 进行维护。此外,我们发现 LLEC 在反应的第 12 天分离时主要来自 KLRG1+ 效应细胞。我们的工作挑战了 KLRG1+CD127low 群体由短寿命细胞主导的概念,并表明 KLRG1 下调不是成为长寿命保护性记忆 T 细胞的先决条件。我们还发现,与 KLRG1+ 效应细胞相比,LLEC 会进行稳态增殖,并且不会严重依赖 IL-15 进行维护。此外,我们发现 LLEC 在反应的第 12 天分离时主要来自 KLRG1+ 效应细胞。我们的工作挑战了 KLRG1+CD127low 群体由短寿命细胞主导的概念,并表明 KLRG1 下调不是成为长寿命保护性记忆 T 细胞的先决条件。我们还发现,与 KLRG1+ 效应细胞相比,LLEC 会进行稳态增殖,并且不会严重依赖 IL-15 进行维护。此外,我们发现 LLEC 在反应的第 12 天分离时主要来自 KLRG1+ 效应细胞。我们的工作挑战了 KLRG1+CD127low 群体由短寿命细胞主导的概念,并表明 KLRG1 下调不是成为长寿命保护性记忆 T 细胞的先决条件。
更新日期:2020-07-01
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