Search results for "Tolerance induction"
showing 10 items of 38 documents
Regulation of IgE production and airway reactivity by CD4(-)CD8(-) regulatory T cells
2015
The mechanisms of tolerance induction occurring in the course of allergen-specific immunotherapy have not been elucidated in full detail. Our study aimed to characterize high zone tolerance in mouse models of type I allergy and of allergic airway inflammation induced by subcutaneous sensitization of mice with high doses of the model allergen ovalbumin (OVA) without the use of adjuvant. Mice were immunized by subcutaneous injection of high doses (HD) of OVA or, for comparison, low doses (LD) of OVA in saline. HD-mice showed lower specific IgE, but augmented IgG in sera than LD-mice. Pre-treatment of mice with HD-OVA antigen-specifically inhibited IgE production subsequently induced by LD-OVA…
MitoKATP-channel opener protects against neuronal death in rat venous ischemia.
2005
OBJECTIVE: Mitochondrial adenosine triphosphate-dependent potassium (mitoK ATP ) channels are present in the brain, and several reports have shown their neuroprotective, preconditioning effect against an ischemic insult. The role of mitoK ATP channels in the penumbra area has not been studied thoroughly. In a model of venous ischemia, widespread penumbra-like low flow areas are created, which are susceptible to cortical spreading depression. Thus, we studied effects of mitoK ATP channels on infarct size in this model. METHODS: Male Wistar rats were subjected to two-vein occlusion by photochemical thrombosis of two adjacent cortical veins combined with KCI-induced cortical spreading depressi…
A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes.
2018
Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)-mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+ regulatory T cell (Treg) induction in vitro. Accordingly, Treg induction is improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas alter…
Low zone tolerance induced by systemic application of allergens inhibits TC1-mediated skin inflammation
2005
Background The induction of tolerance may be a promising target of strategies aimed at preventing harmful allergic diseases. Low zone tolerance (LZT), induced by epicutaneous application of low doses of contact allergens, inhibits the development of T C 1-mediated contact hypersensitivity (CHS). Objective We evaluated the effect of systemic (oral, intravenous) administration of low amounts of haptens on specific immune reactions and tolerance induction. Methods By using the mouse model of LZT, we analyzed immune reactions in vivo (skin inflammation) and T-cell responses in vitro after oral, intravenous, or epicutaneous application of low amounts of the contact allergen 2,4,6-trinitro-1-chlo…
PD-1 signalling in CD4+T cells restrains their clonal expansion to an immunogenic stimulus, but is not critically required for peptide-induced tolera…
2010
Summary The ultimate outcome of T-cell recognition of peptide–major histocompatibility complex (MHC) complexes is determined by the molecular context in which antigen presentation is provided. The paradigm is that, after exposure to peptides presented by steady-state dendritic cells (DCs), inhibitory signals dominate, leading to the deletion and/or functional inactivation of antigen-reactive T cells. This has been utilized in a variety of models providing peptide antigen in soluble form in the absence of adjuvant. A co-inhibitory molecule of considerable current interest is PD-1. Here we show that there is the opportunity for the PD-1/PD-L1 interaction to function in inhibiting the T-cell r…
Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma.
1997
Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma-derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83+ DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemo-immunotherapy. rDCs were 5 times more potent inducers of allogeneic T-cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed prod…
Residents'corner April 2014. Editorial: what's new this month?
2014
In this issue of the European Journal of Dermatology, Bircher et al.[1] revisit tolerance induction in drug hypersensitivity reactions, which is a controversial issue, particularly in delayed hypersensitivity reactions. Drug hypersensitivity may present as a mild, moderate or severe life-threatening reaction, becoming a problem for many patients when the offending drug is essential (and even irreplaceable).Determining which drug is responsible for the reaction may be challenging, especially in multiple [...]
A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of preterm labor during pregnancy and in the induction of organ rejectio…
2010
Regulatory T cells (Tregs) are known to suppress alloimmune responses during pregnancy and post organ transplantation. We demonstrate that a distinct subset of FoxP3(+)DR(+)-Tregs among the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool is critically involved in preterm labor induction and kidney transplant rejection as well. Compared to healthy pregnancies and non-rejecting kidney recipients, we found that the percentage of the FoxP3(+)DR(+)-Treg subset was not reduced, but that the level of HLA-DR expression of such Tregs was strongly diminished in preterm laboring women and in patients with acute renal allograft rejection. In addition, both patient collectives showed a significantly red…
Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells
2011
Background Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). Methodology/Principal Findings IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an…
Induction of inflammatory cytokines in murine keratinocytes upon in vivo stimulation with contact sensitizers and tolerizing analogues
1992
In order to elucidate the role of keratinocytes (KCs) in the induction of contact sensitivity, we applied various contact sensitizers [2,4-dinitrofluorobenzene (DNFB), urushiol, 3-n-pentadecylcatechol (PDC), 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone)] and tolerizing compounds [2,4-dinitrothiocyanobenzene (DNTB), 5-methyl-3-n-pentadecyl-catechol (5-Me-PDC)] onto the earskin of non-sensitized Balb/c mice. In addition, we applied croton oil as a non-sensitizing, but stimulatory agent. Cytokine production was demonstrated by Northern blot hybridization of the total cellular RNA extracted from epidermal cells depleted by Langerhans cells and Thy 1+ dendritic cells using radiolabeled DNA …