期刊
JCI INSIGHT
卷 5, 期 11, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.132963
关键词
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资金
- US Department of Veterans Affairs [51K2CX001471-03]
- NIH [HL134544, AI076174, AI069501]
- San Diego Primary Infection Resource Consortium (NIH) [AI106039]
- Translational Virology Core at the San Diego Center for AIDS Research [AI036214]
- Richard J. Fasenmyer Foundation
- CWRU CFAR Catalytic and Developmental Awards [AI036219]
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 CO57(+)C1328(-) phenotype. The cytokine IL-15 promotes the phenotype, survival, and proliferation of CX3CR1(+)VD57(+)CD8(+) Tmem in vitro, whereas T cell receptor stimulation leads to their death. IL-15-driven survival is dependent on STATS and Bcl-2 activity, and IL-15-induced proliferation requires STATS 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.
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