Comparison of morphology, phenotypes and function between cultured human IL-4-DC and IFN-DC

Abstract

Dendritic cells (DCs) as professional antigen presenting cells, are important in the initiation of the primary immune response. The present study compared the morphology, phenotypes and function between monocyte-derived human DCs produced from a conventional culturing system containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 (IL-4-DC) and DCs generated by the stimulation of GM-CSF and interferon (IFN)-α (IFN-DC). When compared with IL-4-DC in morphology, IFN-DC contained more organelles, including endoplasmic reticulum and myelin figures, whereas mature (m)IL-4-DC contained more vacuoles in the cells. The spikes of IFN-DC were shorter and thicker. The expression of phenotypes between immature IFN-DC and IL-4-DC were diverse. Following maturation with tumor necrosis factor-α, IFN-DC and IL-4-DC upregulated the expression of cluster of differentiation (CD) 11c and CD83. Conversely, immature IFN-DC and IL-4-DC secreted few inflammatory cytokines including interleukin (IL)-18, IL-23, IL-12p70, IL-1β and anti-inflammatory IL-10. Following maturation, large amounts of the cytokines were secreted by these two DCs and mIFN-DC secreted more cytokines compared with mIL-4-DC in general. Furthermore, immature IFN-DC and IL-4-DC loaded with cytomegalovirus (CMV)-pp65 protein were unable to induce the priming of T cells, as evaluated by the intracellular staining with IFN-γ. Notably, mature DCs exhibited the ability to present CMV-pp65 protein and activate T cells. The mIFN-DC activated a greater proportion of autologous CD4+ T cells (0.91 vs. 0.31%, P<0.001) and CD8+ T cells (0.90 vs. 0.48%, P<0.001) to secret IFN-γ compared with mIL-4-DC. The results suggested that the morphology, phenotypes and cytokine secretion of IFN-DC and IL-4-DC were diverse. The mIFN-DC were more effective in priming and cross-priming T cells when compared with IL-4-DC.

Analysis of the Expression and Prognosis for Leukocyte Immunoglobulin-Like Receptor Subfamily B in Human Liver Cancer

“…Based on the KEGG results and previous researches [33][34][35] , we hypothesized that LILRB family members and their related genes are involved in the pathways of antigen processing and presentation and natural killer cell-mediated cytotoxicity (Fig. 10A and 10B).…”

Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy

“…IFN-α can stimulate differentiation of CD14 + monocytes in DCs jointly with GM-CSF (Gabriele et al, 2004) which will be discussed below. IFN-α/GM-CSF stimulation leads to the increased expression of HLA-DR, CD11c, CD83, B7 costimulatory molecules CD80 and CD86, including on DCs of cancer patients, and such DCs are able to efficiently present an antigen to CD4 + and CD8 + T-cells (Paquette et al, 2002;Jin et al, 2017). However, IFN-β reduces the ability of mature DCs to stimulate T-cell proliferation and differentiate into IFNγ-producing Th1 cells (Yen et al, 2010).…”

Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α

“…При этом нами получены новые данные о меньшей стимуляторной активности DC Сore/NS3 на продукцию IL-4/IL-6 по сравнению со способностью активировать секрецию IFNγ и их высокой способности к индукции цитотоксических Т-клеток. Эффективность IFN-DC, нагруженных усеченными HCV Core-и NS3антигенами, может быть обусловлена большей эффективностью IFN-DC в кросс-презентации длинноразмерных пептидов, презентации вирусных белков и индукции вирусспецифических цитотоксических Т-клеток [2,8,12,25].…”