Search results for "antigen"
showing 10 items of 3420 documents
Targeting CD52 does not affect murine neuron and microglia function.
2020
The humanized anti-CD52 antibody alemtuzumab is successfully used in the treatment of multiple sclerosis (MS) and is thought to exert most of its therapeutic action by depletion and repopulation of mainly B and T lymphocytes. Although neuroprotective effects of alemtuzumab have been suggested, direct effects of anti-CD52 treatment on glial cells and neurons within the CNS itself have not been investigated so far. Here, we show CD52 expression in murine neurons, astrocytes and microglia, both in vitro and in vivo. As expected, anti CD52-treatment caused profound lymphopenia and improved disease symptoms in mice subjected to experimental autoimmune encephalomyelitis (EAE). CD52 blockade also …
Gatekeeper role of brain antigen‐presenting CD11c + cells in neuroinflammation
2015
Multiple sclerosis is the most frequent chronic inflammatory disease of the CNS. The entry and survival of pathogenic T cells in the CNS are crucial for the initiation and persistence of autoimmune neuroinflammation. In this respect, contradictory evidence exists on the role of the most potent type of antigen-presenting cells, dendritic cells. Applying intravital two-photon microscopy, we demonstrate the gatekeeper function of CNS professional antigen-presenting CD11c(+) cells, which preferentially interact with Th17 cells. IL-17 expression correlates with expression of GM-CSF by T cells and with accumulation of CNS CD11c(+) cells. These CD11c(+) cells are organized in perivascular clusters…
The future of Extracellular Vesicles as Theranostics – an ISEV meeting report
2020
ABSTRACT The utilization of extracellular vesicles (EVs) in clinical theranostics has rapidly advanced in the past decade. In November 2018, the International Society for Extracellular Vesicles (ISEV) held a workshop on “EVs in Clinical Theranostic”. Here, we report the conclusions of roundtable discussions on the current advancement in the analysis technologies and we provide some guidelines to researchers in the field to consider the use of EVs in clinical application. The main challenges and the requirements for EV separation and characterization strategies, quality control and clinical investigation were discussed to promote the application of EVs in future clinical studies.
T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita
2016
AbstractT cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) – characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells – a process facilitated by T cell receptor (…
Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape.
2019
Abstract Foxp3+ regulatory T cells (Tregs) sustain immune homeostasis and may contribute to immune escape in malignant disease. As a prerequisite for developing immunologic approaches in cancer therapy, it is necessary to understand the ontogeny and the antigenic specificities of tumor-infiltrating Tregs. We addressed this question by using a λ-MYC transgenic mouse model of endogenously arising B-cell lymphoma, which mirrors key features of human Burkitt lymphoma. We show that Foxp3+ Tregs suppress antitumor responses in endogenous lymphoma. Ablation of Foxp3+ Tregs significantly delayed tumor development. The ratio of Treg to effector T cells was elevated in growing tumors, which could be …
Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A
2016
Psoriasis is a common chronic inflammatory skin disease restricted to humans. The understanding of its pathogenesis has long been hampered by the lack of suitable chronic mouse models. The cytokine IL-17A has emerged as a key player in epithelial immune responses and the defense against extracellular pathogens. Moreover, enhanced expression of IL-17A can turn pathologic and is closely associated with psoriasis. In this study, we generated a novel transgenic mouse model that recapitulates many characteristics of psoriasis. DC-1L-17A(ind) mice with constitutive low-level expression of IL-17A by CD11c(+) cells gradually develop skin lesions during adult life. The lesions preferentially occur a…
Clinical efficacy of α4 integrin block with natalizumab in ankylosing spondylitis
2016
We describe the impact of α4-β1/7 blockade with natalizumab, a recombinant humanised immunoglobulin (Ig) G4κ monoclonal antibody (mAb) targeted to the α4 subunit of the α4β1 and α4β7 integrins, on the gut and spine inflammation in a patient with ankylosing spondylitis (AS) who developed multiple sclerosis after treatment with tumour necrosis factor (TNF)-blocking agents. A 45-year-old man with human leucocyte antigen (HLA)-B27-positive AS was admitted in January 2007. He had been diagnosed with AS 4 years earlier based on the presence of inflammatory back pain, peripheral arthritis, radiographic bilateral grade 2 sacroiliitis, HLA-B27 positivity. At that time, he had evidence of chronic int…
IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection
2016
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD4…
Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-con…
2015
BACKGROUND Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS. METHODS In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals. RESUL…
Autoimmune aspects in glaucoma
2016
The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in glaucoma patients. Furthermore we found antibody deposits in human glaucomatous retinae in a pro-inflammatory environment. Clinical studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies belong to the natural autoimmunity. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also neuroprotective characteristics and influence the protein expression …