Normalization of natural killer cell function and phenotype with effective anti-HIV therapy and the role of IL-10.
OBJECTIVE
Natural killer (NK) cell function is likely to be important in controlling HIV infection and opportunistic pathogens. We therefore evaluated NK function and phenotype over the course of antiretroviral therapy (ART) and examined the potential mechanisms of altered NK activity in HIV infection.


METHODS
We measured NK cell percentage, NK cytolytic activity (both by flow cytometry) and plasma IL-10 concentrations (by enzyme-linked immunosorbent assay) in 10 HIV-seropositive patients before and over one year of effective ART. To examine potential mechanisms of altered NK activity, we measured NK receptor expression in ART treated and untreated HIV-positive individuals by flow cytometry. As IL-10 enhances NK activity, we studied the effect of IL-10 on NK receptor expression and activity in peripheral blood mononuclear cells (PBMC) from HIV-seronegative individuals.


RESULTS
NK cytolytic activity was elevated in HIV infection and decreased with ART to levels observed in HIV-negative individuals. A greater proportion of NK cells from untreated HIV-positive individuals expressed the NK receptors CD158a and CD161 than either HIV-negative volunteers or effectively treated HIV-positive patients. NK cells from PBMC incubated with IL-10 demonstrated increases in CD158a, CD161 and CD94 expression and increases in cytolytic activity. The treatment-associated decrease in NK activity paralleled a decrease in IL-10 production.


CONCLUSIONS
The observation that IL-10 alters NK receptor expression similar to that observed in HIV infection, and the fact that NK receptor expression and activity normalize in parallel with ART-induced reduction of circulating IL-10 levels supports a role for IL-10 in NK cell activity and HIV immunopathogenesis.
Parato
Karl G
KG
Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Kumar
Ashok
A
Badley
Andrew D
AD
Sanchez-Dardon
Jaime L
JL
Chambers
Kelley A
KA
Young
Charlene D
CD
Lim
Wilfred T
WT
Kravcik
Stephen
S
Cameron
D William
DW
Angel
Jonathan B
JB
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D012367:RNA, Viral / Q000032:analysis; D011971:Receptors, Immunologic / Q000378:metabolism
D019380:Anti-HIV Agents; D012367:RNA, Viral; D011971:Receptors, Immunologic; D016753:Interleukin-10