Oliva A, Kinter AL, Rubbert A, Vaccarezza M, Fauci AS; National Institutes of Health, Bethesda, MD.
MIP-1alpha, MIP-1beta and RANTES inhibit replication of macrophage-tropic strains of HIV-1. We analyzed chemokine production in various purified peripheral blood mononuclear cell (PBMC) subpopulations from HIV-infected individuals. We found that natural killer (NK) cells are potent producers of beta-chemokines, particularly after stimulation with IL-2 and alphaCD16. Therefore, we tested the ability of NK cells to suppress viral replication in cocultures of CD8/NK-depleted PBMC isolated from HIV-infected individuals to which autologous NK cells were added. NK cells inhibited viral replication to a degree comparable to that of CD8+ T cells as determined by RT or p24 assays. Triggering of CD16 is essential for this effect, as no suppression was observed when NK cells were purified by negative selection or by CD56 selection only. In the majority of patients tested we could abrogate the suppression of virus by adding neutralizing antibodies to MIP-1alpha, MIP-1beta and RANTES. These data demonstrate that activated NK cells are potent suppressors of HIV replication/spread and that this effect is in part mediated by beta-chemokines.
Keywords: AEGIS, Chemokines, CC, Virus Replication, Killer Cells, Natural, HIV-1, Macrophage Inflammatory Protein-1, RANTES, T-Lymphocytes, Macrophages, Chemokines, Interleukin-2, Receptors, IgG, Anti-HIV Agents, Human, virology, AIDS
