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Journal of Virology, March 2006, p. 2529-2538, Vol. 80, No. 5
0022-538X/06/$08.00+0 doi:10.1128/JVI.80.5.2529-2538.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Sarah Rowland-Jones,
Hilton Whittle, and
Assan Jaye*
MRC Laboratories, Fajara, Banjul, The Gambia
Received 20 October 2005/ Accepted 7 December 2005
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/µl) and in 50 HIV-uninfected control subjects. Lytic activity and gamma interferon (IFN-
) 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-1ß, RANTES, tumor necrosis factor alpha, and IFN-
produced by NK CD56bright 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.
Present address: RIVM, Bilthoven, The Netherlands.
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