Abstract
BackgroundA subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.ResultsUsing CD7 as an additional NK cell marker, we found that CD3negCD56negCD16+ cells are a heterogeneous population comprised of CD7+ NK cells and CD7neg non-classical myeloid cells. CD7+CD56negCD16+ NK cells are significantly expanded in HIV-1 infection. CD7+CD56negCD16+ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7+CD56+CD16+ NK cells. CD7+CD56neg NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7+CD56+ NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7+CD56negCD16+ NK cells may have recently engaged target cells. Furthermore, CD7+CD56negCD16+ NK cells have significantly increased expression of CD95, a marker of NK cell activation.ConclusionsTaken together, CD7+CD56negCD16+ NK cells are activated, mature NK cells that may have recently engaged target cells.
Highlights
A subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic Human immunodeficiency virus-1 (HIV-1) infection
CD56negCD16+ cells are a mixed population of myeloid and NK cells that is expanded during chronic HIV-1 infection
A significant decrease in the frequency of CD56brightCD16neg and CD56+CD16+ NK cells with a significant increase in the frequency of CD56negCD16+ cells was observed in HIV-1-infected subjects, during chronic HIV1 infection (Figure 1A)
Summary
A subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. Natural killer (NK) cells comprise 5–20% of peripheral blood mononuclear cells (PBMC) in humans and play a fundamental role in the defense against viral infections, as well as in tumor surveillance, and help shape adaptive immune responses through their production of cytokines [1,2,3]. In HIV-1-infected subjects, CD3negCD56negCD16+ cells are described as having decreased expression of activating receptors (i.e. NKp30 and NKp46) and increased expression of inhibitory receptors (i.e. LIR-1 and inhibitory KIR), and have poor cytolytic, proliferative, and cytokine-producing capabilities [8,9,10,11,12,13,14]. It has been hypothesized that the expansion of this defective CD3negCD56negCD16+ population might be one mechanism by which HIV-1 subverts the NK cell response
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