Combinations of IFN-γand IL-4 induce distinct profiles of dendritic cell-associated immunoregulatory properties

Abstract

Interferon gamma (IFN-g) and interleukin-4 (IL-4) are not only generated during cell-mediated immunity (CMI) and humoral immunity (HI), but are also generated by innate immune cells in response to pathogenic factors. How these cytokines differentially effect the development of dendritic cell (DC)-associated immunoregulatory properties from progenitor cells during innate immunity is unresolved. To address this we have utilized a homogeneous DC progenitor-like cell line, MTHC-D2, as a model to examine cytokine-induced maturation of DCs. By 6 h IFN-g induced genes that are important for antiviral activity and development of CMI, whereas IL-4 induced genes involved in cellular adhesion, uptake of extracellular antigen, suppression of cytotoxic T-cell responses, and that repair the extracellular matrix. By 48 h the cytokine stimulus had induced many properties characteristic of immature DCs; however, these were differentially effected by IFN-g and IL-4. IFN-g induced the greatest levels of costimulatory/ activation marker expression, and the highest levels of T-cell proliferation, whereas IL-4 induced the greatest levels of phagocytic activity. Stimulation of the cells with CD40 Ab enhanced the levels of costimulatory marker expression and T-cell stimulatory capacity of cells exposed to IFN-g, but had little effect on cells exposed to IL-4 in the absence of IFN-g.

Jacalin capped platinum nanoparticles confer persistent immunity against multiple Aeromonas infection in zebrafish

“…This is an interesting observation, since IL-4 is vital for promoting Th2 responses 42–44 and is equally important for B cell growth and development 45 . However, IL-4 is anti-inflammatory and is well known to inhibit the production of pro-inflammatory cytokines such as IL-1β and TNF-α 43 and antagonizes IFN-γ 46 .…”

Aberrancies in the differentiation and maturation of dendritic cells from bone-marrow precursors are linked to various genes on chromosome 4 and other chromosomes of the BB-DP rat

“…However, IL-4 was added to our cultures, but IFNg was not. This cytokine stimulates DC to upregulate co-stimulatory/activation markers and the cell's capability to stimulate T cells [41]. Macrophage-like cells are also present in our DC cultures and OX7 C bone-marrow precursors can also give rise to macrophages, if stimulated appropriately with M-CSF.…”

“…A T cell factor that could account for an appropriate DC differentiation from precursors could be an essential interaction with the co-stimulatory CD40L on T cells present in the culture; CD40L is able to induce a final differentiation of DC [37,38]. Also T cell cytokines such as IL-4 [39,40] and IFNg [41,42] might play a role. However, IL-4 was added to our cultures, but IFNg was not.…”

TNF-αPromotes IFN-γ-Induced CD40 Expression and Antigen Process in Myb-Transformed Hematological Cells

“…The MTHCs used in this study were prepared from C3H mouse using the same method as described previously [23]. The MTHCs were maintained in modified IMEM medium (Invitrogen) containing 50 unit/mL of GM-CSF and 10% fetal calf serum (FCS).…”

“…Mouse GM-CSF, IL-4, and IFN- γ were produced in insect Sf9 cells by infecting the cells with baculovirus expressing the corresponding genes. The concentrations were titered as described previously [23]. Mouse TNF- α was purchased from Sigma and was stored at −80°C in small aliquots until use.…”