Search results for "inflammation"

Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution

2016

Rationale: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. Objective: This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. Methods and Results: CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effect…

Opposing functions of thymic stromal lymphopoietin–responsive basophils and dendritic cells in a mouse model of atopic dermatitis

2015

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…

Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.

2011

Background Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine. Objective In this study we developed a human PBMC–engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms. Methods Nonobese diabetic (NOD)– scid -γc −/− mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically. Results Using the aeroallergens birch or gra…

MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4

2015

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functi…

Soluble GARP has potent antiinflammatory and immunomodulatory impact on human CD4+ T cells

2013

Glycoprotein A repetitions predominant (GARP) is expressed on the surface of activated human regulatory T cells (Treg) and regulates the bioavailability of transforming growth factor-β (TGF-β). GARP has been assumed to require membrane anchoring. To investigate the function of GARP in more detail, we generated a soluble GARP protein (sGARP) and analyzed its impact on differentiation and activation of human CD4⁺ T cells. We demonstrate that sGARP efficiently represses proliferation and differentiation of naïve CD4⁺ T cells into T effector cells. Exposure to sGARP induces Foxp3, decreases proliferation and represses interleukin (IL)-2 and interferon-γ production, resulting in differentiation …

The role of CD8+ T cells and their local interaction with CD4+ T cells in myelin oligodendrocyte glycoprotein35-55-induced experimental autoimmune en…

2013

Abstract T cells have an essential role in the induction of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Although for CD4+ T cells it is well established that they contribute to the disease, less is known about the role of CD8+ T cells. Our aim was to determine the individual contribution of CD4+ and CD8+ T cells in myelin oligodendrocyte glycoprotein (MOG)35–55–induced EAE. We investigated MOG35–55–activated CD8+ T cells to clarify their potential to induce or attenuate EAE. We monitored the behavior of CD8+ T cells and their interaction with CD4+ T cells directly at the site of inflammation in the CNS using intravital imaging of the brainstem of…

Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity

2012

Background IL-10–treated dendritic cells (DCs) have been shown to inhibit T-cell responses through induction of anergy and regulatory T cells in various model systems, including allergic inflammation, but the factors being involved in this inhibition are still unclear. Objective This study set out to analyze such factors produced or induced by IL-10–treated DCs by using gene expression profiling and to explore their function. Methods CD4 + T cells from allergic donors were stimulated with autologous monocyte-derived allergen-pulsed mature DCs or IL-10–treated DCs. After 24 hours, the transcriptional profile was analyzed by using Affymetrix technology. Results were validated by using quantit…

Perforin deficiency attenuates inflammation and tumor growth in colitis-associated cancer

2010

Background: Patients with inflammatory bowel disease (IBD) have a markedly increased risk to develop colon cancer, but there are only limited data about the host antitumor response in such colitis-associated cancer. In the present study we aimed at assessing the role of perforin-dependent effector mechanisms in the immune response in a murine model of colitis-associated colon cancer. Methods: Wildtype and perforin-deficient mice were analyzed in a mouse model of colitis-associated colon cancer using azoxymethane (AOM) and dextran sodium sulfate (DSS). Results: Tumors of wildtype mice showed infiltration of CD4+, CD8+ T cells, natural killer (NK) cells, high numbers of apoptotic cells, and e…

Analysis of parathyroid graft rejection suggests alloantigen-specific production of nitric oxide by iNOS-positive intragraft macrophages

2009

Abstract Background During acute rejection of organ or tissue allografts T cells and macrophages are dominant infiltrating cells. CD4-positive T cells are important for the induction of allograft rejection and macrophages are important effector cells mediating cytotoxicity via production of nitric oxide (NO) by the inducible NO-synthase (iNOS). In the present study we analysed whether the destruction of primarily nonvascularised parathyroid allografts is also mediated by iNOS-positive macrophages. Methods Hypocalcaemic Lewis rats received parathyroid isografts (from Lewis donors) and allografts (from Wistar Furth donors), respectively, under the kidney capsule. Levels of serum calcium above…