Article number 158
Antigens, CD56--analysis; HIV Infections--immunology; Killer Cells, Natural--chemistry; Killer Cells, Natural--immunology; Receptors, IgG--analysis
BACKGROUND: 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.
RESULTS: 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 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⁺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.
CONCLUSIONS: Taken together, CD7⁺CD56(neg)CD16⁺ NK cells are activated, mature NK cells that may have recently engaged target cells.
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Milush, J. M., López-Vergès, S., York, V. A., Deeks, S. G., Martin, J. N., Hecht, F. M., … Nixon, D. F. (2013). CD56negCD16+ NK cells are activated mature NK cells with impaired effector function during HIV-1 infection. Retrovirology, 10, 158. doi:10.1186/1742-4690-10-158
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