RT Journal Article SR Electronic T1 Differential Regulation of Human Blood Dendritic Cell Subsets by IFNs JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 2961 OP 2969 DO 10.4049/jimmunol.166.5.2961 VO 166 IS 5 A1 Ito, Tomoki A1 Amakawa, Ryuichi A1 Inaba, Muneo A1 Ikehara, Susumu A1 Inaba, Kayo A1 Fukuhara, Shirou YR 2001 UL http://www.jimmunol.org/content/166/5/2961.abstract AB 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-αβ)-producing cells. Here, we investigate the effects of IFN-αβ and IFN-γ as well as other cytokines on CD11c+ and CD11c− DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-γ and IFN-α, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c+ DCs. Incubation of CD11c+ DCs with IFN-γ also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-α did not induce IL-12 but, rather, augmented IL-10 production. IFN-α-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-α 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-α, 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-γ, and IL-4. Thus, CD11c+ and CD11c− DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.