Differential Regulation of Human Blood Dendritic Cell Subsets by IFNs

Abstract

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.

Qualitatively distinct patterns of cytokines are released by human dendritic cells in response to different pathogens

“…32,44 Studies with LPS and whole bacteria have shown that they too can induce production of this key initiator of immune responses. [33][34][35][36][37] Previously published work using live Mycobacterium tuberculosis and human DCs 37,54 suggest that in this experimental model, large amounts of IFN-a are produced, but in our assay using fixed bacteria this was not seen, suggesting that surface ligation of extracellular receptors may have effects that are different from those seen during intracellular replication. Figure 8.…”

Study on immune function of dendritic cells in patients with esophageal carcinoma

“…The importance of the CD80/CD86-CD28 system in T cell responses has been well demonstrated [10,20,21,29] . The CD80 and CD86, members of the immunoglobulin super gene family, are encoded by separate genes and provide costimulatory function for APC-dependent T-cell activation both in vivo and in vitro [25][26][27][28] . A previous study reported that most tumor tissues, like those from the nonhematopoietic origin, did not express costimulatory molecules, which would render T cells unresponsive for the specific antigens [20] .…”

Roles of toll-like receptors in natural interferon-producing cells as sensors in immune surveillance

“…Most myeloid DCs have some capacity to produce IL-12 and, thereby, to induce Th1 development. However, this capacity varies with the conditions of their maturational stage or stimulation delivered to DCs [43][44][45][46][47][48]. A similar functional plasticity is observed in IPC-derived DCs [8, 49 -51].…”