Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15.
JCI Insight
; 5(11)2020 06 04.
Article
em En
| MEDLINE
| ID: mdl-32369455
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
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Linfócitos T CD8-Positivos
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Antígenos CD57
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Interleucina-15
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Receptor 1 de Quimiocina CX3C
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Memória Imunológica
Limite:
Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos