Lysis of HIV-1-infected autologous CD4+ primary T cells by interferon-alpha-activated NK cells requires NKp46 and NKG2D
C Tomescu, D Mavilio, LJ Montaner - Aids, 2015 - journals.lww.com
C Tomescu, D Mavilio, LJ Montaner
Aids, 2015•journals.lww.comObjective: 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-α). Design: The goal of the present study is
to identify the specific NK-activating receptors involved in NK lysis of aHIV+ CD4 following …
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-α). Design: The goal of the present study is
to identify the specific NK-activating receptors involved in NK lysis of aHIV+ CD4 following …
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-α).
Design:
The goal of the present study is to identify the specific NK-activating receptors involved in NK lysis of aHIV+ CD4 following IFN-α 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-α-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-α (median 2280 pg/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< 0.01, n= 8) and NKG2D (P< 0.05, n= 8), but not 2B4, NTBA, NKp30 or NKp44, significantly reduced IFN-α-activated lysis of aHIV+ CD4.
Conclusions:
Taken together, these results demonstrate that endogenous levels of IFN-α secreted by plasmacytoid dendritic cells induce NK cells to lyse aHIV+ CD4 via the engagement of NKp46 and NKG2D.
Lippincott Williams & Wilkins