TIGIT is upregulated by HIV-1 infection and marks a highly functional adaptive and mature subset of natural killer cells

Elena Vendrame, Christof Seiler, Thanmayi Ranganath, Nancy Q Zhao, Rosemary Vergara, Michel Alary, Annie-Claude Labbé, Fernand Guédou, Johanne Poudrier, Susan Holmes, Michel Roger, Catherine A Blish*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)801-813
Number of pages13
JournalAids
Volume34
Issue number6
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • adaptive
  • HIV
  • mature
  • natural killer cells
  • T cell immunoreceptor with Ig and ITIM domains (TIGIT)
  • NK CELLS
  • GAMMA PRODUCTION
  • CUTTING EDGE
  • MEMORY
  • PVR
  • IMMUNODEFICIENCY
  • IMMUNOGLOBULIN
  • ACTIVATION
  • POPULATION
  • RESPONSES

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