In:
AIDS, Ovid Technologies (Wolters Kluwer Health), Vol. 34, No. 6 ( 2020-05-1), p. 801-813
Abstract:
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. Design and Methods: 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). Results: 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 hi , NKG2C hi , LILRB1 hi , FcRγ lo , Syk lo ). 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. Conclusion: 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.
Type of Medium:
Online Resource
ISSN:
0269-9370
,
1473-5571
DOI:
10.1097/QAD.0000000000002488
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
detail.hit.zdb_id:
2012212-3
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