Search results for "Lymphocyte"

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…

Cylindromatosis (Cyld) gene mutation in T cells promotes the development of an IL-9-dependent allergic phenotype in experimental asthma

2016

Cylindromatosis (CYLD) is a ubiquitously expressed deubiquitinating enzyme which removes activating ubiquitin residues from important signaling molecules of the NF-κB pathway. In CYLDex7/8 transgenic mice, a naturally occurring short isoform (sCYLD) is overexpressed in the absence of full length CYLD, leading to excessive NF-κB activity. Herein, we investigated the impact of the CYLDex7/8 mutation selectively in T cells on the development of experimental allergic airway disease induced by sensitization and challenge with ovalbumin. Compared with their wildtype littermates, mice bearing the T cell-specific mutation (CD4+CYLDex7/8) display stronger eosinophilia and mucus production in the lun…

Human T cells in silico: Modelling their electrophysiological behaviour in health and disease

2016

Although various types of ion channels are known to have an impact on human T cell effector functions, their exact mechanisms of influence are still poorly understood. The patch clamp technique is a well-established method for the investigation of ion channels in neurons and T cells. However, small cell sizes and limited selectivity of pharmacological blockers restrict the value of this experimental approach. Building a realistic T cell computer model therefore can help to overcome these kinds of limitations as well as reduce the overall experimental effort. The computer model introduced here was fed off ion channel parameters from literature and new experimental data. It is capable of simu…

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

2015

A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells

2017

A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine ind…

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 …

Immunelectronmicroscopic characterization of T4 and T8 lymphocytes and natural killer cells in neuronal ceroid-lipofuscinosis.

1995

CD4+, CD8+, and CD56+ cells were isolated with the immunomagnetic separation technique from peripheral blood mononuclear cells (PBMC) of 3 patients with neuronal ceroid-lipofuscinosis : one patient each with infantile (INCL), late infantile (LINCL), and juvenile (JNCL) neuronal ceroid-lipofuscinoses, all studied by light (LM) and electron (EM) microscopy. To compare the pathology of these cells with affected cells in other types of lysosomal diseases, the separation was also performed with PBMC of 1 patient with mucolipidosis (ML) type II, 2 patients with mucopolysaccharidosis (MPS) type I, and 4 patients with MPS type III. Disease-specific lysosomal inclusions were identified in CD4+, CD8+…

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…

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

2003

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…

T-cell receptor transfer into human T cells with ecotropic retroviral vectors

2014

Adoptive T-cell transfer for cancer immunotherapy requires genetic modification of T cells with recombinant T-cell receptors (TCRs). Amphotropic retroviral vectors (RVs) used for TCR transduction for this purpose are considered safe in principle. Despite this, TCR-coding and packaging vectors could theoretically recombine to produce replication competent vectors (RCVs), and transduced T-cell preparations must be proven free of RCV. To eliminate the need for RCV testing, we transduced human T cells with ecotropic RVs so potential RCV would be non-infectious for human cells. We show that transfection of synthetic messenger RNA encoding murine cationic amino-acid transporter 1 (mCAT-1), the re…