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The Journal of Immunology, 2001, 166: 2961-2969.
Copyright © 2001 by The American Association of Immunologists

Differential Regulation of Human Blood Dendritic Cell Subsets by IFNs1

Tomoki Ito2,*, Ryuichi Amakawa*, Muneo Inaba{dagger}, Susumu Ikehara{dagger}, Kayo Inaba{ddagger} and Shirou Fukuhara*

* First Department of Internal Medicine and {dagger} First Department of Pathology, Kansai Medical University, Osaka, Japan; and {ddagger} Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan

Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a+/CD11c+ population (CD11c+ DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a-/CD11c- population (CD11c- DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-{alpha}{beta})-producing cells. Here, we investigate the effects of IFN-{alpha}{beta} and IFN-{gamma} as well as other cytokines on CD11c+ and CD11c- DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-{gamma} and IFN-{alpha}, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c+ DCs. Incubation of CD11c+ DCs with IFN-{gamma} also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-{alpha} did not induce IL-12 but, rather, augmented IL-10 production. IFN-{alpha}-primed matured CD11c+ DCs induced IL-10-producing regulatory T cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-{alpha} by itself neither matured CD11c- DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c- DCs. Unlike IFN-{alpha}, IL-3 was a potent survival factor and induced the maturation of CD11c- DCs. The IL-3-primed CD11c- DCs activated T cells to produce IL-10, IFN-{gamma}, and IL-4. Thus, CD11c+ and CD11c- DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.




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