CD56 super(neg)CD16 super(+) NK cells are activated mature NK cells with impaired effector function during HIV-1 infection

Background: A subset of CD3 super(neg)CD56 super(neg) CD16 super(+) 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. Results: Using CD7 as an additional NK cell marker, we found that CD3 super(neg)CD56 super(neg) CD16 super(+) cells are a heterogeneous population comprised of CD7 super(+) NK cells and CD7 super(neg) non-classical myeloid cells. CD7 super(+)CD56 super(neg)CD 16 super(+) NK cells are significantly expanded in HIV-1 infection. CD7 super(+)CD56 super(neg)CD 16 super(+) NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7 super(+)CD56 super(+)CD16 super(+) NK cells. CD7 super(+)CD56 super(neg) NK cells in healthy donors produced minimal IFN[gamma] following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7 super(+)CD56 super(+) NK cells. HIV-1 infection resulted in reduced IFN[gamma] 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 super(+)CD56 super(neg)CD 16 super(+) NK cells may have recently engaged target cells. Furthermore, CD7 super(+)CD56 super(neg)CD 16 super(+) NK cells have significantly increased expression of CD95, a marker of NK cell activation. Conclusions: Taken together, CD7 super(+)CD56 super(neg)CD 16 super(+) NK cells are activated, mature NK cells that may have recently engaged target cells.