Document Type
Journal Article
Publication Date
1-2013
Journal
Retrovirology
Volume
Volume 10
Inclusive Pages
Article number 158
Keywords
Antigens, CD56--analysis; HIV Infections--immunology; Killer Cells, Natural--chemistry; Killer Cells, Natural--immunology; Receptors, IgG--analysis
Abstract
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
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
Peer Reviewed
1
Open Access
1
Gating strategy to identify NK cell subsets in a representative healthy donor
CD7 gating allows precise identification of NK cells.pdf (300 kB)
CD7 gating allows precise identification of NK cells
Comparison of NK cell gating strategies on NKp30 and NKp46 expression.pdf (263 kB)
Comparison of NK cell gating strategies on NKp30 and NKp46 expression
Comments
Reproduced with permission of BioMed Central. Retrovirology.