Search results for "Dendritic cells."
showing 10 items of 360 documents
Suppressor activity of anergic T cells induced by IL-10-treated human dendritic cells: association with IL-2- and CTLA-4-dependent G1 arrest of the c…
2003
We have previously shown that human IL-10-treated dendritic cells (DC) induce an antigen-specific anergy in CD4+ T lymphocytes. These anergic T cells are characterized by an inhibited proliferation, a reduced production of IL-2, and additionally display antigen-specific suppressor activity. In this study we investigated the mechanisms underlying the anergic state and regulatory function of these T cells. We did not observe enhanced rates of programmed cell death of anergic CD4+ suppressor T cells compared to T cells stimulated with mature DC. Cell cycle analysis by DNA staining and Western blot experiments revealed an arrest of anergic CD4+ T suppressor cells in the G1 phase. High levels of…
Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells
2011
Abstract Human mature dendritic cells (DCs) can efficiently stimulate natural killer (NK)–cell responses without being targeted by their cytotoxicity. To understand this important regulatory crosstalk, we characterized the development of the immunologic synapse between mature DCs and resting NK cells. Conjugates between these 2 innate leukocyte populations formed rapidly, persisted for prolonged time periods and matured with DC-derived f-actin polymerization at the synapse. Polarization of IL-12 and IL-12R to the synapse coincided with f-actin polymerization, while other activating and inhibitory molecules were enriched at the interface between DCs and NK cells earlier. Functional assays re…
Prophylactic and therapeutic intervention in IgE responses by biolistic DNA vaccination primarily targeting dendritic cells.
2005
Background Allergen gene transfer represents an alternative approach to specific immunotherapy with allergen extracts. Gene gun–mediated DNA immunization with plasmid vectors expressing a transgene under control of the promoter of the fascin gene (pFascin) allows for antigen production predominantly by dendritic cells and resulted in the generation of CD8 + cytotoxic T lymphocytes as well as in the development of a type 1 immune response. Objective We compared the in vivo efficiency of biolistic transfection with pFascin and plasmids containing the cytomegalovirus promoter (pCMV) in a mouse model of type I allergy. Methods BALB/c mice were sensitized with the model allergen β-galactosidase …
Different regulation of T helper 1- and T helper 2-promoting cytokine signalling factors in human dendritic cells after exposure to protein versus co…
2008
Cytokine-dependent T helper 1 (Th1) differentiation versus T helper 2 (Th2) differentiation is controlled by distinct transcription factors. Previously, we have demonstrated that immature human dendritic cells (DC) from blood donors with allergies show rapid phosphorylation of the Th2-associated signal transducer and activator of transcription 6 (STAT6) upon contact with protein allergens. In the present study we investigated whether this process is regulated by the downstream molecules suppressor of cytokine signalling (SOCS) and/or by the factors T-bet and GATA3. Therefore, immature DC of grass or birch pollen-allergic donors were treated with the respective Th2-promoting protein allergen…
Cyclic adenosine monophosphate and IL-10 coordinately contribute to nTreg cell-mediated suppression of dendritic cell activation
2010
In humans and mice naturally occurring regulatory T cells (nTregs) are crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Here we show that co-culture of murine dendritic cells (DC) and nTregs results in an immediate increase of cAMP in DC, responsible for a rapid down-regulation of co-stimulatory molecules (CD80, CD86). In addition, the inhibitory surface molecule B7-H3 on DC is up-regulated. Subsequently, nTreg-derived IL-10 inhibits the cytokine production (IL-6, IL-12) of suppressed DC therewith preserving their silent phenotype. Hence, our data indicate that nTreg…
Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin-10-treated dendri…
2006
Summary Background In grass pollen-allergic individuals, T cell anergy can be induced by IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg) suppressing the function of other T cells in the periphery. As transforming growth factor (TGF)-β is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-β-treated T cells in this system. Materials and Methods Freshly isolated CD4+ or CD4+CD25− T cells from grass pollen-allergic donors were stimulated with autologous mature monocyte-de…
Nucleic acid recognizing Toll-like receptors and autoimmunity
2007
The understanding of autoimmune diseases experienced an impressive boost since the Toll-like receptors (TLRs) have been identified as possible key players in autoimmune pathophysiology. Although these receptors recognize a variety of structures derived from viruses, bacteria, and fungi leading to subsequent initiation of the relevant immune responses, recent data support the idea that TLRs are crucial in the induction and perpetuation of certain autoimmune diseases, especially the systemic lupus erythematosus (SLE). In this review, we will summarize recent data on involvement of TLRs in the development of autoimmune diseases. We will focus on TLRs 7, 8, and 9 that were originally identified…
Mast Cells Are Key Promoters of Contact Allergy that Mediate the Adjuvant Effects of Haptens
2011
SummaryA prominent feature of sensitizing environmental compounds that cause allergic contact dermatitis is the rapid induction of an innate inflammatory response that seems to provide danger signals for efficient T cell priming. We generated mouse models of mast cell deficiency, mast cell-specific gene inactivation, and mast cell reporter mice for intravital imaging and showed that these adjuvant effects of contact allergens are mediated by mast cells and histamine. Mast cell deficiency resulted in impaired emigration of skin DCs to the lymph node and contact hypersensitivity was dramatically reduced in the absence of mast cells. In addition, mast cell-specific inactivation of the Il10 gen…
Impaired Th1 responses in mice deficient in Epstein-Barr virus-induced gene 3 and challenged with physiological doses of Leishmania major.
2005
Protection against Leishmania major is dependent on IL-12 release from L. major-infected dendritic cells (DC) that induce IFN-gamma-producing Th1/Tc1 cells. IL-27, a novel member of the IL-12 family, is a heterodimer composed of p28 and IL-12p40-related Epstein-Barr virus-induced gene 3 (EBI3), and was shown to be produced by DC. In this study, we utilized EBI3-deficient mice to investigate the role of IL-27 in leishmaniasis using physiological low-dose infections that mimic natural transmissions. Lesions in EBI3(-/-) mice were significantly larger between weeks 3 and 10 post infection, reaching up to approximately threefold increased lesion volumes compared to wild types. In parallel, derm…
Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
2019
Background Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called a…