炎性 CX3CR1+CD57+CD8+ T 细胞是由 IL-15 产生和扩增的。
Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15.
机构信息
Center for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
出版信息
JCI Insight. 2020 Jun 4;5(11):132963. doi: 10.1172/jci.insight.132963.
Abstract
HIV infection is associated with an increase in the proportion of activated CD8+ memory T cells (Tmem) that express CX3CR1, but how these cells are generated and maintained in vivo is unclear. We demonstrate that increased CX3CR1 expression on CD8+ Tmem in people living with HIV (PLWH) is dependent on coinfection with human CMV, and CX3CR1+CD8+ Tmem are enriched for a putatively immunosenescent CD57+CD28- phenotype. The cytokine IL-15 promotes the phenotype, survival, and proliferation of CX3CR1+CD57+CD8+ Tmem in vitro, whereas T cell receptor stimulation leads to their death. IL-15-driven survival is dependent on STAT5 and Bcl-2 activity, and IL-15-induced proliferation requires STAT5 and mTORC1. Thus, we identify mechanistic pathways that could explain how "inflammescent" CX3CR1+CD57+ CD8+ Tmem dominate the overall memory T cell pool in CMV-seropositive PLWH and that support reevaluation of immune senescence as a nonproliferative dead end.
摘要
HIV 感染与表达 CX3CR1 的激活的 CD8+ 记忆 T 细胞（Tmem）比例增加有关，但这些细胞在体内如何产生和维持尚不清楚。我们证明，HIV 感染者（PLWH）中 CD8+Tmem 上 CX3CR1 的表达增加依赖于与人巨细胞病毒（CMV）的合并感染，并且 CX3CR1+CD8+Tmem 富含潜在的免疫衰老 CD57+CD28-表型。细胞因子 IL-15 促进体外 CX3CR1+CD57+CD8+Tmem 的表型、存活和增殖，而 T 细胞受体刺激导致其死亡。IL-15 驱动的存活依赖于 STAT5 和 Bcl-2 活性，而 IL-15 诱导的增殖需要 STAT5 和 mTORC1。因此，我们确定了可以解释“炎症性”CX3CR1+CD57+CD8+Tmem 如何在 CMV 血清阳性 PLWH 中主导总体记忆 T 细胞池的机制途径，并支持重新评估免疫衰老作为非增殖性死胡同。
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