Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15.
basic_science · Level V
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- Record sourced from PubMed, PMID 32369455.
- Also identified by DOI 10.1172/jci.insight.132963 and PMC identifier 7346586.
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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.
Medical subject headings
- CD57 Antigens
- CD8-Positive T-Lymphocytes
- CX3C Chemokine Receptor 1
- HIV Infections
- HIV-1
- Immunologic Memory
- Interleukin-15