| Literature DB >> 32369455 |
Stephen R Morris1,2, Bonnie Chen1, Joseph C Mudd3, Soumya Panigrahi1, Carey L Shive2, Scott F Sieg1, Cheryl M Cameron4, David A Zidar2, Nicholas T Funderburg5, Souheil-Antoine Younes1, Benigno Rodriguez1, Sara Gianella6, Michael M Lederman1, Michael L Freeman1.
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.Entities:
Keywords: AIDS/HIV; Cellular immune response; Immunology; T cells
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Year: 2020 PMID： 32369455 PMCID： PMC7346586 DOI： 10.1172/jci.insight.132963
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708