Search results for "Autoimmunity"
showing 10 items of 349 documents
Anti-Inflammatory Action of Heterogeneous Nuclear Ribonucleoprotein A2/B1 in Patients with Autoimmune Endocrine Disorders
2019
Our previous studies documented that human fibroblast-limbal stem cells (f-LSCs) possess immunosuppressive capabilities, playing a role in regulating T-cell activity. This study highlights the molecular activities by which human f-LSCs can attenuate the inflammatory responses of self-reactive peripheral blood mononuclear cells (PBMCs) collected from patients with autoimmune endocrine diseases (AEDs). Anti-CD3 activated PBMCs from twenty healthy donors and fifty-two patients with AEDs were cocultured on f-LSC monolayer. 2D-DIGE proteomic experiments, mass spectrometry sequencing and functional in vitro assays were assessed in cocultured PBMCs. We identified the downmodulation of several huma…
Advances on Cellular Clonotypic Immunity in Amyotrophic Lateral Sclerosis.
2022
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease, characterized by the progressive degeneration of the upper and lower motor neurons in the cortex and spinal cord. Although the pathogenesis of ALS remains unclear, evidence concerning the role of the clonotypic immune system is growing. Adaptive immunity cells often appear changed in number, or in terms of their activation profiles, both peripherally and centrally; however, their role in ALS appears conflictive. Data from human and animal model studies, which are currently reported in the literature, show that each subset of lymphocytes and their mediators may mediate a protective or toxic mechanism in ALS, affecting both…
A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo
2018
Genetic engineering of T cells with a T cell receptor (TCR) targeting tumor antigen is a promising strategy for cancer immunotherapy. Inefficient expression of the introduced TCR due to TCR mispairing may limit the efficacy and adversely affect the safety of TCR gene therapy. Here, we evaluated the safety and therapeutic efficiency of an optimized single-chain TCR (scTCR) specific for an HLA-A2.1-restricted (non-mutated) p53(264–272) peptide in adoptive T cell transfer (ACT) models using our unique transgenic mice expressing human p53 and HLA-A2.1 that closely mimic the human setting. Specifically, we showed that adoptive transfer of optimized scTCR-redirected T cells does not induce on-tar…
Chronic inflammatory cardiomyopathy of interferon γ-overexpressing transgenic mice is mediated by tumor necrosis factor-α.
2011
We recently described a model of inflammatory cardiomyopathy in interferon (IFN)-γ overexpressing transgenic mice stably circulating IFN-γ in the serum referred to as SAP–-IFN-γ mice. SAP–IFN-γ transgenic mice show cardiac infiltration by mononuclear leukocytes, culminating in dilated cardiomyopathy characterized by an increase of left ventricular end diastolic diameter and reduction of fractional shortening. We hypothesized that the pathological mechanism underlying SAP–IFN-γ cardiomyopathy might be mediated by (auto)immune processes or tumor necrosis factor (TNF)-α synthesis from IFN-γ–activated macrophages. To verify these hypotheses, we crossed SAP–IFN-γ transgenic mice with immunodefic…
Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment.
2021
Celiac disease (CeD) is a frequent immune-mediated disease that affects not only the small intestine but also many extraintestinal sites. The role of gluten proteins as dietary triggers, HLA-DQ2 or -DQ8 as major necessary genetic predisposition, and tissue transglutaminase (TG2) as mechanistically involved autoantigen, are unique features of CeD. Recent research implicates many cofactors working in synergism with these key triggers, including the intestinal microbiota and their metabolites, nongluten dietary triggers, intestinal barrier defects, novel immune cell phenotypes, and mediators and cytokines. In addition, apart from HLA-DQ2 and -DQ8, multiple and complex predisposing genetic fact…
Immunological alterations in hepatitis C virus infection
2013
A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjogren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will out…
Anti-rat liver microsomal and cytosolic antibodies in hepatitis C virus infection.
1994
In order to assess the frequency of autoimmunity markers in hepatitis C virus infection, 229 RIBA 2 HCV positive individuals were tested by ELISA and Immunoblot assay using as antigen rat liver microsomal and cytosolic proteins. Twenty-one out of 229 individuals (9%) showed anti-rat liver microsome antibodies by ELISA, but the titre was low (1:100 to 1:1,600). In Immunoblot, only 5 of these 21 ELISA positive sera recognized also rat liver microsomal proteins (MW between 30 to 64 kDa). Antibodies against rat liver cytosolic proteins were found by ELISA in 14 out of 229 individuals (6%). Three of them showed a reactivity in Immunoblot to 42 kDa or 55 kDA proteins. In conclusion, HCV infection…
T cell receptor Vβ chain restriction and preferred CDR3 motifs of liver-kidney microsomal antigen (LKM-1)-reactive T cells from autoimmune hepatitis …
2001
Aims/Background : The liver-kidney-microsomal antigen (LKM-1) has been recognized as a major CD4 + T cell antigen in autoimmune hepatitis (AIH). The aim of this study was to characterize the antigen recognition sites of the variable T cell receptor β-chain (TCRBV) of T cells specific to LKM-1. Methods: By repeated stimulation of T cells with a recombinant LKM-1 antigen or an LKM-derived peptide followed by limited dilution, we generated T cell clones. Usage of TCRBV was analyzed by RT-PCR and CDR3 antigen recognition sites were sequenced. Results: The 18 LKM-1 specific T cell clones isolated from six AIH patients preferentially expressed the TCR elements BV9, BV5S2+S3, BV6, and BV13S1. Four…
Antimitochondrial antibody -M2 positive autoimmune hepatitis during standard of care for chronic hepatitis C
2012
The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated-interferon (PEG-IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe a severe, acute-onset antimitochondrial antibody (AMA)-M2 positive AIH appearing during the last weeks of SoC in a woman with chronic hepatitis C and no previous history of autoimmunity, and resolving on protracted steroids. In this context, the relevance of the characterization of the immunoglobulin isotype of portal plasma cells for …
Suppression of murine experimental autoimmune hepatitis by T-cell vaccination or immunosuppression
1998
Patients with autoimmune hepatitis (AIH) usually require immunosuppressive therapy for many years, if not for a lifetime. Experimental immunotherapy such as T-cell vaccination aims at manipulating the immune system in such a way that autoimmunity is specifically regulated to enable long-lasting correction of the disease process. We aimed to test the feasibility of T-cell vaccination as well as conventional immunosuppression in the murine model of experimental autoimmune hepatitis (EAH). EAH was induced in 5- to 7-week-old BALB/c mice by immunization with syngeneic liver homogenate in complete Freund's adjuvant. For T-cell vaccination, splenocytes were removed from animals 14 days after indu…