A subset of CD3negCD56negCD16+ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection, and 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 CD3negCD56negCD16+ cells are a mixed population of CD7+ NK cells and CD7neg myeloid cells. CD7+CD56negCD16+ NK cells are significantly expanded in HIV-1 infection. CD7+CD56negCD16+ NK cells are mature and express KIRs, NKG2A, NKG2C, and natural cytotoxicity receptors similar to CD7+CD56+CD16+ cells. CD7+CD56neg NK cells in healthy donors produced minimal IFNg following K562 target cell or IL-12 plus IL-18 stimulation; however, they did degranulate in response to K562 cells similar to CD7+CD56+ NK cells. HIV-1 infection resulted in reduced IFNg 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, suggests that CD7+CD56negCD16+ NK cells may have recently engaged target cells. CD7+CD56negCD16+ NK cells have increased expression of the aging-related cyclin-dependent kinase inhibitors p16/INK4a and p21/Waf1. Taken together, CD7+CD56negCD16+ NK cells appear to be mature NK cells generated from chronic target engagement.
- Copyright © 2013 by The American Association of Immunologists, Inc.