Natural killer cells from HIV-1+ patients produce C-C chemokines and inhibit HIV-1 infection.
Human NK cells have been shown to produce cytokines (e.g., IFN-gamma and TNF-alpha) and the chemokine macrophage inflammatory protein (MIP)-1alpha following stimulation with the combination of two monokines, IL-15 plus IL-12. The C-C chemokines MIP-1alpha, MIP-1beta, 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-1alpha, MIP-1beta, and RANTES protein, in vitro. Further, supernatants of monokine-activated NK cells obtained from both normal donors and AIDS patients showed potent (routinely > or = 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 C-C chemokines MIP-1alpha, MIP-1beta, 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 C-C 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.
Fehniger
T A
TA
Department of Internal Medicine, Ohio State University, Columbus 43210, USA.
Herbein
G
G
Yu
H
H
Para
M I
MI
Bernstein
Z P
ZP
O'Brien
W A
WA
Caligiuri
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000096:biosynthesis*; D006679:HIV Seropositivity / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000276:immunology
D019742:Chemokines, CC