Lysis of HIV-1-infected Autologous CD4+ primary T cells by interferon-alpha-activated NK cells requires NKp46 and NKG2D

Costin Tomescu, Domenico Mavilio, Luis J. Montaner

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Autologous HIV-1-infected CD4+ primary T cells (aHIV+CD4) have been shown to be largely resistant to natural killer (NK)-cell-mediated lysis because of viral strategies of immune evasion. We have previously shown that a preactivation of NK cells with plasmacytoid dendritic cells can significantly augment lysis of aHIV+CD4 through a mechanism dependent on interferon-alpha (IFN-a). Design: The goal of the present study is to identify the specific NK-activating receptors involved in NK lysis of aHIV+CD4 following IFN-a activation. Methods: Peripheral blood mononuclear cells (PBMC) were incubated with aHIV+CD4 to induce the secretion of endogenous levels of IFN-α and drive NK activation. We then utilized a standard chromium lysis assay to assess the degree of IFN-a-activated lysis of aHIV+CD4 in the presence or absence of masking antibodies to a panel of NK-activating receptors and co-receptors. Results: Direct recognition of HIV-1-infected, but not uninfected, autologous CD4+ primary T cells by PBMC induced the secretion IFN-a (median 2280pg/ml, P<0.001, n = 9) that, in turn, activated NK cells (P<0.001, n = 12) and significantly increased their cytolytic potential against aHIV+CD4 (P<0.01, n = 12). The masking of NKp46 (P+CD4. Conclusions: Taken together, these results demonstrate that endogenous levels of IFN-a secreted by plasmacytoid dendritic cells induce NK cells to lyse aHIV+CD4 via the engagement of NKp46 and NKG2D.

Original languageEnglish
Pages (from-to)1767-1773
Number of pages7
JournalAIDS (London, England)
Volume29
Issue number14
DOIs
Publication statusPublished - 2015

Keywords

  • AIDS
  • Cytotoxicity
  • Interferon-alpha
  • NK cells
  • NKG2D
  • NKp46

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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