CD56negCD16? NK cells are activated mature NK cells with impaired effector function during HIV-1 infection.

ABSTRACT: A subset of CD3(neg)CD56(neg)CD16? 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.Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16? cells are a heterogeneous population comprised of CD7? NK cells and CD7(neg) non-classical myeloid cells. CD7?CD56(neg)CD16? NK cells are significantly expanded in HIV-1 infection. CD7?CD56(neg)CD16? 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?CD56(neg) NK cells in healthy donors produced minimal IFN? 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 IFN? 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?CD56(neg)CD16? NK cells may have recently engaged target cells. Furthermore, CD7?CD56(neg)CD16? NK cells have significantly increased expression of CD95, a marker of NK cell activation.Taken together, CD7?CD56(neg)CD16? NK cells are activated, mature NK cells that may have recently engaged target cells.

SUBMITTER: Milush JM 

PROVIDER: S-EPMC3892122 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature