The Journal of Experimental Medicine
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Published online 17 July 2000.
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© The Rockefeller University Press, 0022-1007/2000/7/219/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 2, July 17, 2000 219-226

Original Article

Natural Interferon {alpha}/β–Producing Cells Link Innate and Adaptive Immunity

Norimitsu Kadowakia, Svetlana Antonenkoa, Johnson Yiu-Nam Laub, and Yong-Jun Liua

a Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304
b Department of Antiviral Therapy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033
DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304.650-496-1200650-496-1157

yliu{at}dnax.org

Innate immune responses to pathogens critically impact the development of adaptive immune responses. However, it is not completely understood how innate immunity controls the initiation of adaptive immunities or how it determines which type of adaptive immunity will be induced to eliminate a given pathogen. Here we show that viral stimulation not only triggers natural interferon (IFN)-{alpha}/β–producing cells (IPCs) to produce vast amounts of antiviral IFN-{alpha}/β but also induces these cells to differentiate into dendritic cells (DCs). IFN-{alpha}/β and tumor necrosis factor {alpha} produced by virus-activated IPCs act as autocrine survival and DC differentiation factors, respectively. The virus-induced DCs stimulate naive CD4+ T cells to produce IFN-{gamma} and interleukin (IL)-10, in contrast to IL-3–induced DCs, which stimulate naive CD4+ T cells to produce T helper type 2 cytokines IL-4, IL-5, and IL-10. Thus, IPCs may play two master roles in antiviral immune responses: directly inhibiting viral replication by producing large amounts of IFN-{alpha}/β, and subsequently triggering adaptive T cell–mediated immunity by differentiating into DCs. IPCs constitute a critical link between innate and adaptive immunity.

Key Words: dendritic cells • interferon {alpha}/β–producing cells • innate immunity • adaptive immunity • T cells

N. Kadowaki's present address is Dept. of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Abbreviations used in this paper: DCs, dendritic cells; IPCs, natural IFN-{alpha}/β–producing cells.

© 2000 The Rockefeller University Press


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