Inflammescent CX3CR1+CD57+CD8+ T cells are generated and expanded by IL-15.
AIDS/HIV
Cellular immune response
Immunology
T cells
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
received:
23
08
2019
accepted:
30
04
2020
pubmed:
6
5
2020
medline:
19
5
2021
entrez:
6
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32369455
pii: 132963
doi: 10.1172/jci.insight.132963
pmc: PMC7346586
doi:
pii:
Substances chimiques
CD57 Antigens
0
CX3C Chemokine Receptor 1
0
CX3CR1 protein, human
0
IL15 protein, human
0
Interleukin-15
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI069501
Pays : United States
Organisme : CSRD VA
ID : IK2 CX001471
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI076174
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD094646
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI069501
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL134544
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI036214
Pays : United States
Organisme : NIAID NIH HHS
ID : R24 AI106039
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI036219
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131385
Pays : United States
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