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. 2020 May 1;34(6):801-813.
doi: 10.1097/QAD.0000000000002488.

TIGIT Is Upregulated by HIV-1 Infection and Marks a Highly Functional Adaptive and Mature Subset of Natural Killer Cells

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Free PMC article

TIGIT Is Upregulated by HIV-1 Infection and Marks a Highly Functional Adaptive and Mature Subset of Natural Killer Cells

Elena Vendrame et al. AIDS. .
Free PMC article

Abstract

Objective: 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, 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.

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.

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