Search results for "Regulatory"
showing 10 items of 740 documents
IL-27 improves migrational and antiviral potential of CB dendritic cells.
2013
Abstract Interleukin (IL)-27 is known to be increased considerably in cord blood (CB) dendritic cells (DCs) after TLR ligation. Previously, we demonstrated that also basal IL-27 levels are higher in CB DCs. Here, we examined effects of IL-27 on monocyte derived dendritic cells (moDCs) to approach its particular role in the specialized immune system of the human neonate. Exogenous IL-27 promotes IL-27 transcription in CB and adult blood (AB) moDCs. IL-27 acts on CB moDCs primarily by significantly augmenting IL-27 protein, secondarily by increasing transcription of CXCL10 among other chemokines, chemokine receptor CCR1, interferon stimulated genes, transcription factor IRF8 and genes involve…
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…
Exclusive transduction of human CD4+ T Cells upon systemic delivery of CD4-targeted lentiviral vectors
2015
Abstract Playing a central role in both innate and adaptive immunity, CD4+ T cells are a key target for genetic modifications in basic research and immunotherapy. In this article, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4+ cells by surface engineering. When applied to PBMCs, CD4-LV transduced CD4+ but not CD4− cells. Notably, also unstimulated T cells were stably genetically modified. Upon systemic or intrasplenic administration into mice reconstituted with human PBMCs or hematopoietic stem cells, reporter gene expression was predominantly detected in lymphoid organs. Evaluation of GFP expression in organ-derived cells and blood …
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…
In vitro generation of CD4+CD25+ regulatory cells from murine naive T cells
2007
CD4+ CD25+ regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Recent data indicate that Tregs not only develop in the thymus during ontogeny but can also differentiate from naive T cells in the periphery. The following protocol describes a method by which Tregs are generated in vitro by stimulation of naive T cells in the presence of transforming growth factor beta (Ti-Tregs). In vitro-induced regulatory T cells express markers of conventional Treg such as CD25 and the genetic program committing transcription factor FoxP3. Functionally the in vitro-generated Ti-Tregs suppress T-cell activation and proliferation while in vivo these cells have been proven t…
CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes
2013
CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25hi Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25 hi Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+…
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 …
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…
Regulatory T Cells Accumulate and Proliferate in the Ischemic Hemisphere for up to 30 Days after MCAO
2012
Local and peripheral immune responses are activated after ischemic stroke. In our present study, we investigated the temporal distribution, location, induction, and function of regulatory T cells (Tregs) and the possible involvement of microglia, macrophages, and dendritic cells after middle cerebral artery occlusion (MCAO). C57BL/6J and Foxp3EGFP transgenic mice were subjected to 30 minutes MCAO. On days 7, 14, and 30 after MCAO, Tregs and antigen presenting cells were analyzed using fluorescence activated cell sorting multicolor staining and immunohistochemistry. A strong accumulation of Tregs was observed on days 14 and 30 in the ischemic hemisphere accompanied by the elevated presence …
The Regulatory T Cell Family: Distinct Subsets and their Interrelations
2003
The immune system, a highly effective and dynamic cellular network, protects a host from pathogens. Therefore, the immune system must distinguish self from nonself structures, but also between harmful and innocuous foreign Ags to prevent nonessential and self-destructive immune responses. The