0000000000286220

AUTHOR

Juergen Knop

Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells

AbstractCoupling of ovalbumin (OVA) to anti–DEC-205 monoclonal antibody (mAb) (αDEC) induced the proliferation of OVA-specific T cells in vivo. Expansion was short-lived, caused by dendritic cells (DCs), and rendered T cells anergic thereafter. Phenotypic analysis revealed the induction of CD25+/CTLA-4+ T cells suppressing proliferation and interleukin-2 (IL-2) production of effector CD4+ T cells. The findings were supported by 2 disease models: (1) CD4+ T-cell–mediated hypersensitivity reactions were suppressed by the injection of αDEC-OVA and (2) the application of hapten-coupled αDEC-205 reduced CD8+ T-cell–mediated allergic reactions. Thus, targeting of antigens to immature DCs through …

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Cytokines and their effects on maturation, differentiation and migration of dendritic cells.

In this review the role of cytokines in the maturation and migration of phenotypically and functionally diverse dendritic cell (DC) subpopulations is discussed and their role in the progress of differentiation from bone marrow progenitors to lymphoid DC is described. GM-CSF is the most important cytokine for the development of functional DC and acts in concert with a varying mixture of other cytokines such as IL-4, IL-1 and TNF-α to direct the development of individual DC subpopulations.

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Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity

Uptake of Leishmania major by dendritic cells (DCs) results in activation and interleukin (IL)-12 release. Infected DCs efficiently stimulate CD4- and CD8- T cells and vaccinate against leishmaniasis. In contrast, complement receptor 3-dependent phagocytosis of L. major by macrophages (MPhi) leads exclusively to MHC class II-restricted antigen presentation to primed, but not naive, T cells, and no IL-12 production. Herein, we demonstrate that uptake of L. major by DCs required parasite-reactive immunoglobulin (Ig)G and involved FcgammaRI and FcgammaRIII. In vivo, DC infiltration of L. major-infected skin lesions coincided with the appearance of antibodies in sera. Skin of infected B cell-de…

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Nonocclusion and Early Reopening of the Great Saphenous Vein After Endovenous Laser Treatment Is Fluence Dependent

Background. Parameters influencing failure and recanalization rates of endovenous laser treatment (ELT) of the great saphenous vein (GSV) are still to be determined. Objective. To evaluate treatment-related parameters of ELT with respect to early failure of occlusion or recanalization of GSVs. Methods. A series of 77 consecutive patients received ELT of 106 GSVs with continuous pullback of the laser fiber. Duplex examination was performed at 1 day, 4 weeks, and 3 months after the procedure. Clinical patient and vessel characteristics as well as technical parameters of the ELT procedure were evaluated via multiple logistic regression analysis. Results. A median vein length of 60 cm (range of…

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Critical role of IL-10 in the induction of low zone tolerance to contact allergens

The development and mechanisms of tolerance to allergens are poorly understood. Using the murine low zone tolerance (LZT) model, where contact hypersensitivity (CHS) is prevented by repeated topical low-dose applications of contact allergens, we show that LZT induction is IL-10 dependent. IL-10 is required for the generation of LZT effector cells, that is, CD8+ regulatory T cells. Only T cells from tolerized IL-10+/+ mice or IL-10-/- mice reconstituted with IL-10 during LZT induction adoptively transferred LZT to naive mice and prevented CHS, whereas T cells from IL-10-/- mice failed to do so. The IL-10 required for normal LZT development is derived from lymph node CD4+ T cells, the only sk…

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Induction of tolerogenic DCs: ‘you are what you eat’

Abstract Dendritic cells (DCs) take up antigens using antigen receptors that can be divided into three major classes: C-type lectins, integrins and Fc receptors. These receptors facilitate effective presentation of MHC–peptide complexes to T cells, resulting in the induction of immune responses. However, we discuss recent evidence that some receptors also cause induction of tolerance. Signaling motifs within the receptors either block maturation of DCs or induce signals that render DCs tolerogenic. These DCs then either induce regulatory T cells or cause deletion of effector T cells, resulting in the induction of tolerance. Antigen receptors expressed by DCs might therefore have an importan…

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Activation of MAP kinase p38 is critical for the cell-cycle–controlled suppressor function of regulatory T cells

AbstractRegulatory T cells play an essential role in the control of self-tolerance and processes of adaptive immunity. Tolerogenic IL-10–modulated human dendritic cells (IL-10DCs) induce anergic T cells with strong suppressive properties (iTregs) that inhibit the activation of effector T cells. In this study, we evaluated the interaction between cell-cycle regulation and intracellular signaling in these iTregs. Analysis of signal transduction events revealed a down-regulation of the mitogen-activated protein kinases (MAPKs) Jun N-terminal kinase (JNK) and a nonactivation of extracellular-signal–regulated kinase (ERK) in contrast to a marked activation of p38 MAPK and the p38 effector MAPK-a…

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