scholarly journals Selective Induction of Tumor Necrosis Receptor Factor 6/Decoy Receptor 3 Release by Bacterial Antigens in Human Monocytes and Myeloid Dendritic Cells

2004 ◽  
Vol 72 (1) ◽  
pp. 89-93 ◽  
Author(s):  
Sunghee Kim ◽  
William J. McAuliffe ◽  
Liubov S. Zaritskaya ◽  
Paul A. Moore ◽  
Lurong Zhang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tyrosine Kinases ◽  
Bacterial Infections ◽  
Tumor Necrosis ◽  
Myeloid Dendritic Cells ◽  
Activated T Cells ◽  
Decoy Receptor ◽  
Bacterial Antigens ◽  
Decoy Receptor 3

ABSTRACT Tumor necrosis factor (TNF) receptor 6/decoy receptor 3 (TR6/DcR3) is an antiapoptosis soluble receptor of the TNF family produced by tumor cells. In this study, TR6 expression in human immune cells was investigated. TR6 mRNA and protein were detectable in selected antigen-presenting cells. Monocytes and myeloid-derived dendritic cells (MDC) released the protein exclusively following stimulation of Toll-like receptor 2 (TLR2) and TLR4 by gram-positive and gram-negative bacterial antigens. Plasmacytoid dendritic cells, activated by bacterial antigens via TLR9 or by viral infection, did not produce the protein. Similarly, activated T cells did not release TR6. The release of TR6 by MDC was dependent on the activation of p42/p44 mitogen-activated protein kinases, Src-like protein tyrosine kinases, and phosphatidylinositol 3-kinase, signaling pathways important for MDC maturation and survival. In agreement with the in vitro data, TR6 levels in serum were significantly elevated in patients with bacterial infections. Overall, these data suggest a novel role for TR6 in immune responses to bacteria.

scholarly journals CD14 Expressing Precursors Give Rise to Highly Functional Conventional Dendritic Cells for Use as Dendritic Cell Vaccine

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3818
Author(s):  
Maud Plantinga ◽  
Denise A. M. H. van den Beemt ◽  
Ester Dünnebach ◽  
Stefan Nierkens
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cord Blood ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Activated T Cells

Induction of long-lasting immunity by dendritic cells (DCs) makes them attractive candidates for anti-tumor vaccination. Although DC vaccinations are generally considered safe, clinical responses remain inconsistent in clinical trials. This initiated studies to identify subsets of DCs with superior capabilities to induce effective and memory anti-tumor responses. The use of primary DCs has been suggested to overcome the functional limitations of ex vivo monocyte-derived DCs (moDC). The ontogeny of primary DCs has recently been revised by the introduction of DC3, which phenotypically resembles conventional (c)DC2 as well as moDC. Previously, we developed a protocol to generate cDC2s from cord blood (CB)-derived stem cells via a CD115-expressing precursor. Here, we performed index sorting and single-cell RNA-sequencing to define the heterogeneity of in vitro developed DC precursors and identified CD14+CD115+ expressing cells that develop into CD1c++DCs and the remainder cells brought about CD123+DCs, as well as assessed their potency. The maturation status and T-cell activation potential were assessed using flow cytometry. CD123+DCs were specifically prone to take up antigens but only modestly activated T-cells. In contrast, CD1c++ are highly mature and specialized in both naïve as well as antigen-experienced T-cell activation. These findings show in vitro functional diversity between cord blood stem cell-derived CD123+DC and CD1c++DCs and may advance the efficiency of DC-based vaccines.

scholarly journals Dendritic Cells Pulsed with Intact Streptococcus pneumoniae Elicit both Protein- and Polysaccharide-specific Immunoglobulin Isotype Responses In Vivo through Distinct Mechanisms

2001 ◽  
Vol 195 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Jesus Colino ◽  
Yi Shen ◽  
Clifford M. Snapper
Keyword(s):  
Dendritic Cells ◽  
Streptococcus Pneumoniae ◽  
Myeloid Dendritic Cells ◽  
Bacterial Proteins ◽  
Histocompatibility Complex ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Igg1 Isotype

Immature bone marrow–derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae. After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice. Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype.

Chlamydia trachomatis-infected macrophages induce apoptosis of activated T cells by secretion of tumor necrosis factor-? in vitro

2004 ◽  
Vol 193 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Michael C. Jendro ◽  
Frederik Fingerle ◽  
Tobias Deutsch ◽  
Andrea Liese ◽  
Lars K�hler ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Chlamydia Trachomatis ◽  
Tumor Necrosis ◽  
Activated T Cells ◽  
Necrosis Factor

scholarly journals Interaction of Rotavirus with Human Myeloid Dendritic Cells

2005 ◽  
Vol 79 (23) ◽  
pp. 14526-14535 ◽  
Author(s):  
Carlos F. Narváez ◽  
Juana Angel ◽  
Manuel A. Franco
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Transforming Growth Factor Beta ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Myeloid Dendritic Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Stimulation Of

ABSTRACT We have previously shown that very few rotavirus (RV)-specific T cells that secrete gamma interferon circulate in recently infected and seropositive adults and children. Here, we have studied the interaction of RV with myeloid immature (IDC) and mature dendritic cells (MDC) in vitro. RV did not induce cell death of IDC or MDC and induced maturation of between 12 and 48% of IDC. Nonetheless, RV did not inhibit the maturation of IDC or change the expression of maturation markers on MDC. After treatment with RV, few IDC expressed the nonstructural viral protein NSP4. In contrast, a discrete productive viral infection was shown in MDC of a subset of volunteers, and between 3 and 46% of these cells expressed NSP4. RV-treated IDC secreted interleukin 6 (IL-6) (but not IL-1β, IL-8, IL-10, IL-12, tumor necrosis factor alpha, or transforming growth factor beta), and MDC released IL-6 and small amounts of IL-10 and IL-12p70. The patterns of cytokines secreted by T cells stimulated by staphylococcal enterotoxin B presented by MDC infected with RV or uninfected were comparable. The frequencies and patterns of cytokines secreted by memory RV-specific T cells evidenced after stimulation of peripheral blood mononuclear cells (PBMC) with RV were similar to those evidenced after stimulation of PBMC with RV-infected MDC. Finally, IDC treated with RV strongly stimulated naive allogeneic CD4+ T cells to secrete Th1 cytokines. Thus, although RV does not seem to be a strong maturing stimulus for DC, it promotes their capacity to prime Th1 cells.

In vitro generation of murine myeloid dendritic cells from CD34-positive precursors

2009 ◽  
Vol 33 (7) ◽  
pp. 778-784 ◽  
Author(s):  
Tom-Li Stephen ◽  
Fabian Harms ◽  
Mario Fabri ◽  
Eva Flenner ◽  
Martina Bessler ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Myeloid Dendritic Cells

scholarly journals Activated T Cells Induce Macrophages To Produce NO and Control Leishmania major in the Absence of Tumor Necrosis Factor Receptor p55

2000 ◽  
Vol 68 (3) ◽  
pp. 1428-1434 ◽  
Author(s):  
Michelle Nashleanas ◽  
Phillip Scott
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leishmania Major ◽  
Tumor Necrosis Factor Receptor ◽  
No Production ◽  
Activated T Cells ◽  
Necrosis Factor

ABSTRACT The ability to activate macrophages in vitro for nitric oxide production and killing of Leishmania major parasites is dependent on tumor necrosis factor, although L. major-infected mice lacking the TNF receptor p55 (TNFRp55−/− mice) or both the TNFRp55 and TNFRp75 (TNFRp55p75−/− mice) are able to produce NO in vivo and eliminate the parasites. Here we report that activated T cells cocultured with macrophages results in TNFR-independent activation sufficient to control parasites and that both CD40/CD40L and LFA-1 contribute to T-cell-mediated macrophage activation. Thus, anti-CD3-stimulated T cells activated TNFR-deficient macrophages, while T cells from CD40L−/− mice were partially defective in triggering NO production by TNFRp55p75−/− macrophages. Moreover, in the presence of gamma interferon, anti-CD40 monoclonal antibody (MAb) activated TNFR-deficient macrophages. Finally, MAb blockade of LFA-1 completely inhibited macrophage NO production. Our data indicate that T cells can activate macrophages in the absence of TNF, thus providing a mechanism for how TNFR-deficient mice can control intracellular pathogens.

scholarly journals Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells

2017 ◽  
Vol 25 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Maria Antonietta Mazzola ◽  
Radhika Raheja ◽  
Keren Regev ◽  
Vanessa Beynon ◽  
Felipe von Glehn ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Dimethyl Fumarate ◽  
Nuclear Factor Κb ◽  
Interleukin 17 ◽  
Myeloid Dendritic Cells ◽  
Gm Csf ◽  
Monomethyl Fumarate ◽  
And Function

Background: Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood. Objective: To investigate the role of MMF on human mDCs maturation and function. Methods: mDCs from healthy controls were isolated and cultured in vitro with MMF. The effect of MMF on mDC gene expression was determined by polymerase chain reaction (PCR) array after in vitro MMF treatment. The ability of mDCs to activate T cells was assessed by in vitro co-culture system. mDCs from DMF-treated multiple sclerosis (MS) patients were analyzed by flow cytometry and PCR. Results: MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB. mDCs from DMF-treated MS patients also showed the same immature phenotype. T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells. Conclusion: We report that MMF can modulate immune response by affecting human mDC function.

Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1865-1872 ◽  
Author(s):  
Miriam Merad ◽  
Lawrence Fong ◽  
Jakob Bogenberger ◽  
Edgar G. Engleman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Wild Type Mouse ◽  
Interleukin 12 ◽  
Myeloid Dendritic Cells ◽  
Myeloid Antigens

Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8α+ and CD8α− DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8α, but they do express high levels of myeloid antigens such as CD11b and FcγR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8α but only low levels of myeloid antigens. CD8α+ DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8α− epidermal LC in vivo, it was found that these cells expressed CD8α on migration to the draining LN. Similarly, CD8α− LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8αKO mouse expressed CD8α when they reached the draining LN. The results also show that CD8α+ LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-γ, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8α when they migrate to the draining LN. CD8α expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage.

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