Natural killer cell function is well preserved in asymptomatic human immunodeficiency virus type 2 (HIV-2) infection but similar to that of HIV-1 infection when CD4 T-cell counts fall.
Natural killer (NK) cells are potent effectors of natural immunity and their activity prevents human immunodeficiency virus type 1 (HIV-1) viral entry and viral replication. We sought to determine whether NK immune responses are associated with different clinical course of HIV-1 and HIV-2 infections. A cross-sectional analysis of NK cell responses was undertaken in 30 HIV-1 and 30 HIV-2 subjects in each of three categories of CD4(+)-T-cell counts (>500, 200 to 500, and <200 cells/microl) and in 50 HIV-uninfected control subjects. Lytic activity and gamma interferon (IFN-gamma) secretion were measured by chromium release and enzyme-linked immunospot assays, respectively. Flow cytometry was used to assess intracellular cytokines and chemokines. Levels of NK cytotoxicity were significantly higher in HIV-2 than in HIV-1 infections in subjects with high CD4(+)-T-cell counts and were similar to that of the healthy controls. In these HIV-2 subjects, cytolytic activity was positively correlated to NK cell count and inversely related to plasma viremia. Levels of intracellular MIP-1beta, RANTES, tumor necrosis factor alpha, and IFN-gamma produced by NK CD56(bright) cells were significantly higher in HIV-2- than HIV-1-infected subjects with high CD4(+)-T-cell counts but fell to similar levels as CD4 counts dropped. The data suggest efficient cytolytic and chemokine-suppressive activity of NK cells early in HIV-2 infection, which is associated with high CD4(+) T-cell counts. Enhancement of these functions may be important in immune-based therapy to control HIV disease.
MRC Laboratories, Banjul, The Gambia.
Samuel Victor
SV
Nuvor
Marianne
M
van der Sande
Sarah
S
Rowland-Jones
Hilton
H
Whittle
Assan
A
Jaye
D018791:CD4 Lymphocyte Count; D018925:Chemokines / Q000032:analysis; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology*; D014766:Viremia
D018925:Chemokines; D016207:Cytokines; D007371:Interferon-gamma