TIGIT is upregulated by HIV-1 infection and marks a highly functional adaptive and mature subset of natural killer cells.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
pubmed:
7
2
2020
medline:
23
2
2021
entrez:
7
2
2020
Statut:
ppublish
Résumé
Our objective was to investigate the mechanisms that govern natural killer (NK)-cell responses to HIV, with a focus on specific receptor--ligand interactions involved in HIV recognition by NK cells. We first performed a mass cytometry-based screen of NK-cell receptor expression patterns in healthy controls and HIV individuals. We then focused mechanistic studies on the expression and function of T cell immunoreceptor with Ig and ITIM domains (TIGIT). The mass cytometry screen revealed that TIGIT is upregulated on NK cells of untreated HIV women, but not in antiretroviral-treated women. TIGIT is an inhibitory receptor that is thought to mark exhausted NK cells; however, blocking TIGIT did not improve anti-HIV NK-cell responses. In fact, the TIGIT ligands CD112 and CD155 were not upregulated on CD4 T cells in vitro or in vivo, providing an explanation for the lack of benefit from TIGIT blockade. TIGIT expression marked a unique subset of NK cells that express significantly higher levels of NK-cell-activating receptors (DNAM-1, NTB-A, 2B4, CD2) and exhibit a mature/adaptive phenotype (CD57, NKG2C, LILRB1, FcRγ, Syk). Furthermore, TIGIT NK cells had increased responses to mock-infected and HIV-infected autologous CD4 T cells, and to PMA/ionomycin, cytokine stimulation and the K562 cancer cell line. TIGIT expression is increased on NK cells from untreated HIV individuals. Although TIGIT does not participate directly to the response to HIV-infected cells, it marks a population of mature/adaptive NK cells with increased functional responses.
Identifiants
pubmed: 32028328
doi: 10.1097/QAD.0000000000002488
pmc: PMC7148170
mid: NIHMS1557490
pii: 00002030-202005010-00001
doi:
Substances chimiques
Receptors, Immunologic
0
TIGIT protein, human
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
801-813Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007502
Pays : United States
Organisme : NIAID NIH HHS
ID : DP2 AI112193
Pays : United States
Organisme : NIDA NIH HHS
ID : DP1 DA046089
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI138640
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001084
Pays : United States
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