Natural killer cells from HIV-1+ patients produce CC chemokines and inhibit HIV-1 infection

TA Fehniger, G Herbein, H Yu, MI Para… - The Journal of …, 1998 - journals.aai.org
TA Fehniger, G Herbein, H Yu, MI Para, ZP Bernstein, WA O'Brien, MA Caligiuri
The Journal of Immunology, 1998journals.aai.org
Human NK cells have been shown to produce cytokines (eg, IFN-γ and TNF-α) and the
chemokine macrophage inflammatory protein (MIP)-1α following stimulation with the
combination of two monokines, IL-15 plus IL-12. The CC chemokines MIP-1α, MIP-1β, and
RANTES have been identified as the major soluble macrophage-tropic HIV-1-suppressive
factors produced by CD8+ T cells, which exert their action at the level of viral entry. Here, we
demonstrate that monokine-activated NK cells, isolated from both normal and HIV-1+ …
Abstract
Human NK cells have been shown to produce cytokines (eg, IFN-γ and TNF-α) and the chemokine macrophage inflammatory protein (MIP)-1α following stimulation with the combination of two monokines, IL-15 plus IL-12. The CC chemokines MIP-1α, MIP-1β, and RANTES have been identified as the major soluble macrophage-tropic HIV-1-suppressive factors produced by CD8+ T cells, which exert their action at the level of viral entry. Here, we demonstrate that monokine-activated NK cells, isolated from both normal and HIV-1+ donors, produce similar amounts of MIP-1α, MIP-1β, and RANTES protein, in vitro. Further, supernatants of monokine-activated NK cells obtained from both normal donors and AIDS patients showed potent (routinely≥ 90%) suppressive activity against HIV-1 replication in vitro, compared with unstimulated control supernatants. NK cell supernatants inhibited both macrophage-tropic HIV-1 NFN-SX and T cell-tropic HIV-1 NL4–3 replication in vitro, but not dual-tropic HIV-1 89.6. Importantly, the CC chemokines MIP-1α, MIP-1β, and RANTES were responsible only for a fraction of the HIV-1-suppressive activity exhibited by NK cell supernatants against macrophage-tropic HIV-1. Collectively these data indicate that NK cells from normal and HIV-1+ donors produce CC chemokines and other unidentified factors that can inhibit both macrophage-and T cell-tropic HIV-1 replication in vitro. Since NK cells can be expanded in patients with HIV-1, AIDS, and AIDS malignancy in vivo, this cell type may have an important role in the in vivo regulation of HIV-1 infection.
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