Fehniger T A, Herbein G, Yu H, Para M I, Bernstein Z P, O'Brien W A, Caligiuri M A
Department of Internal Medicine, Ohio State University, Columbus 43210, USA.
J Immunol. 1998 Dec 1;161(11):6433-8.
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.
已证明，人自然杀伤细胞（NK细胞）在用两种单核因子（白细胞介素-15加白细胞介素-12）联合刺激后可产生细胞因子（如γ干扰素和肿瘤坏死因子-α）以及趋化因子巨噬细胞炎性蛋白（MIP）-1α。C-C趋化因子MIP-1α、MIP-1β和调节激活正常T细胞表达和分泌的因子（RANTES）已被确定为CD8 + T细胞产生的主要可溶性巨噬细胞嗜性HIV-1抑制因子，它们在病毒进入水平发挥作用。在此，我们证明，从正常和HIV-1阳性供体分离的单核因子激活的NK细胞在体外产生相似量的MIP-1α、MIP-1β和RANTES蛋白。此外，与未刺激的对照上清液相比，从正常供体和艾滋病患者获得的单核因子激活的NK细胞的上清液在体外对HIV-1复制显示出强大的（通常>或= 90%）抑制活性。NK细胞上清液在体外抑制巨噬细胞嗜性HIV-1（NFN-SX）和T细胞嗜性HIV-1（NL4-3）的复制，但不抑制双嗜性HIV-1（89.6）。重要的是，C-C趋化因子MIP-1α、MIP-1β和RANTES仅占NK细胞上清液对巨噬细胞嗜性HIV-1所表现出的HIV-1抑制活性的一部分。这些数据共同表明，来自正常和HIV-1阳性供体的NK细胞产生C-C趋化因子和其他未确定的因子，这些因子可在体外抑制巨噬细胞嗜性和T细胞嗜性HIV-1的复制。由于NK细胞可在体内HIV-1、艾滋病和艾滋病相关恶性肿瘤患者中扩增，这种细胞类型可能在体内HIV-1感染的调节中起重要作用。
