Natural Interferon α/β–Producing Cells Link Innate and Adaptive Immunity

Journal of Experimental Medicine - Tập 192 Số 2 - Trang 219-226 - 2000
Norimitsu Kadowaki1, S. V. Antonenko2, Johnson Yiu‐Nam Lau3, Yong-Jun Liu2
1Department of Immunobiology, DNAX Research Institute of Molecular and Cellular, Biology, Palo Alto, California 94304, USA
2aDepartment of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304
3bDepartment of Antiviral Therapy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033

Tóm tắt

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)-α/β–producing cells (IPCs) to produce vast amounts of antiviral IFN-α/β but also induces these cells to differentiate into dendritic cells (DCs). IFN-α/β and tumor necrosis factor α 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-γ 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-α/β, and subsequently triggering adaptive T cell–mediated immunity by differentiating into DCs. IPCs constitute a critical link between innate and adaptive immunity.

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