Phenotypically and functionally distinct subsets contribute to the expansion of CD56-/CD16+ natural killer cells in HIV infection.
OBJECTIVE
Chronic HIV infection has been associated with activation and increased turnover of natural killer (NK) cells as well as with disturbed homeostasis of the NK cell compartment, including loss of CD56(+) NK cells and accumulation of dysfunctional CD56(-)/CD16(+) NK cells. We performed a comprehensive phenotypical and functional characterization of this population.


METHODS
A cross-sectional study was performed to analyze CD56(-)/CD16(+) NK cells from 34 untreated HIV-infected and 15 seronegative individuals.


METHODS
NK cells were analyzed by flow cytometry. Degranulation was assessed by measuring their expression of CD107a after stimulation with K562 cells, interleukin-12 and interleukin-15.


RESULTS
CD56(-)/CD16(+) NK cells are heterogeneous and composed of two populations, namely CD122(-)/CCR7(+) cells and CD122(-)/CCR7(+) cells. We show that expanded CD122(+) but not CCR7(+) cells in HIV-seropositive individuals are characterized by expression of senescence marker CD57 similarly to CD56(dim)/CD16(+) NK cells along with expression of KIRs, CD8, perforin and granzyme B. Despite expression of perforin and granzyme B, CD57 expressing cells exhibited less numbers of degranulating cells as measured by CD107a, indicating their functional impairment. However, there was no correlation between expansion of total CD56(-)/CD16(+) NK cells or the distinct subpopulations and viral load or CD4 cell count.


CONCLUSIONS
These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(-)/CD16(+) NK cells.
Hong
Henoch S
HS
Klinik für Immunologie und Rheumatologie, Medizinische Hochschule Hannover, Hannover, Germany.
Eberhard
Johanna M
JM
Keudel
Phillip
P
Bollmann
Benjamin A
BA
Ahmad
Fareed
F
Ballmaier
Matthias
M
Bhatnagar
Nupur
N
Zielinska-Skowronek
Margot
M
Schmidt
Reinhold E
RE
Meyer-Olson
Dirk
D
D000328:Adult; D000368:Aged; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D019002:CD56 Antigen / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017452:Receptors, IgG / Q000235:genetics / Q000502:physiology*; D019562:Viral Load; D055815:Young Adult
D015415:Biomarkers; D019002:CD56 Antigen; D017452:Receptors, IgG