A5042350027- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Diabetes and associated disorders
- Monoclonal and Polyclonal Antibodies Research
- Vitamin D Research Studies
- Cell Adhesion Molecules Research
- Adrenal Hormones and Disorders
- CAR-T cell therapy research
- Immune Response and Inflammation
- PI3K/AKT/mTOR signaling in cancer
- Psoriasis: Treatment and Pathogenesis
- NF-κB Signaling Pathways
- Reproductive System and Pregnancy
- Lymphoma Diagnosis and Treatment
- Cystic Fibrosis Research Advances
- Chronic Lymphocytic Leukemia Research
- Atherosclerosis and Cardiovascular Diseases
- Metal and Thin Film Mechanics
- Mycobacterium research and diagnosis
- Blood disorders and treatments
- Liver Diseases and Immunity
- Calcium signaling and nucleotide metabolism
University College London
2015-2024
Roland Hill (United Kingdom)
2018-2024
Institute of Infection and Immunity
2018-2024
The Royal Free Hospital
2013-2022
Newcastle upon Tyne Hospital
2019-2020
Royal Free London NHS Foundation Trust
2018
University of Birmingham
2004-2014
Medical Research Council
2002-2014
UCL Australia
2014
Immune Regulation (United Kingdom)
2003-2013
Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of cell immune responses whose mechanism action the subject debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that can capture its from opposing cells by process trans-endocytosis. After removal, these costimulatory are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via Acquisition CD86 antigen-presenting stimulated receptor engagement...
The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has potent immunomodulatory properties that have promoted its potential use in the prevention and treatment infectious disease autoimmune conditions. A variety immune cells, including macrophages, dendritic activated T cells express intracellular D receptor are responsive to 1,25(OH)(2)D(3.) Despite this, how 1,25(OH)(2)D(3) regulates adaptive immunity remains unclear may involve both direct indirect effects on...
Summary CD4 + CD25 T regulatory cells (T Reg ), suppress antigen‐specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an expressing paternal antigens (the fetus) requiring substantial changes in regulation over a programmed period of time. We analysed whether immune‐suppressive were altered during therefore might play part this tolerant state. The presence was assessed blood 25 non‐pregnant, 63 pregnant seven postnatal healthy women by...
<h3>Rationale</h3> Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but not assessed risk for acute respiratory distress syndrome (ARDS). Causality of these associations never demonstrated. <h3>Objectives</h3> To determine if ARDS is associated with vitamin clinical setting to experimental models influences its severity. <h3>Methods</h3> Human, murine vitro primary alveolar epithelial cell work were included this study....
CD28 and CTLA-4 (CD152) play essential roles in regulating T cell immunity, balancing the activation inhibition of responses, respectively. Although both receptors share same ligands, CD80 CD86, specific requirement for two distinct ligands remains obscure. In present study, we demonstrate that, although targets CD86 destruction via transendocytosis, this process results separate fates itself. presence CD80, remained ligand bound, was ubiquitylated trafficked late endosomes lysosomes....
Abstract Regulatory T cells (Treg) are important in maintaining tolerance to self tissues. As both CD28 and CTLA-4 molecules implicated the function of Treg, we investigated ability their two natural ligands, CD80 CD86, influence Treg-suppressive capacity. During cell responses alloantigens expressed on dendritic cells, observed that Abs against CD86 potently enhanced suppression by CD4+CD25+ Treg. In contrast, blocking proliferative impairing Treg suppression. Intriguingly, relative...
Abstract 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, exerts potent effects on several tissues including cells immune system, where it affects T cell activation, differentiation and migration. The circulating, inactive 25(OH)D3, is generally used as an indication D status. However, use this precursor depends its uptake by subsequent conversion enzyme 25(OH)D3-1α-hydroxylase (CYP27B1) into 1,25(OH)2D3. Using human cells, we show in study that addition 25(OH)D3...
Exceptionally germinal center formation can be induced without T cell help by polysaccharide-based antigens, but these centers involute massive B apoptosis at the time centrocyte selection starts. This study investigates whether cells in cell–independent antigen (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to Ficoll undergo hypermutation their immunoglobulin V region genes. Positive controls are provided comparing same stage of development carrier-primed mice immunized with a...
Significance The inhibitory protein cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is recognized as a crucial regulator of autoimmunity, but its precise mechanism action not yet fully understood. CTLA-4 can down-regulate expression the costimulatory ligands CD80 and CD86 on antigen presenting cells, thereby reducing T-cell CD28 engagement. Here we demonstrate that quantitative changes in level engagement have functional consequences for differentiation toward follicular helper T cells...
CTLA-4 is one of the most important negative regulators T cell immune response. However, subcellular distribution unusual for a receptor that interacts with surface transmembrane ligands in rapidly internalized from plasma membrane. It has been proposed activation can lead to stabilization expression at surface. Here we have analyzed detail internalization, recycling, and degradation CTLA-4. We demonstrate membrane clathrin- dynamin-dependent manner driven by well characterized YVKM...
The strong genetic association between particular HLA alleles and type 1 diabetes (T1D) indicates a key role for CD4+ T cells in disease; however, the differentiation state of responsible is unclear. cell originally was considered dichotomy Th1 Th2 cells, with deemed culpable autoimmune islet destruction. Now, multiple additional fates are recognized distinct roles. Here, we used transgenic mouse model to probe gene expression profile islet-specific by microarray identified clear follicular...
The CTLA-4 pathway is recognized as a major immune inhibitory axis and key therapeutic target for augmenting antitumor immunity or curbing autoimmunity. CTLA-4-deficient mice provide the archetypal example of dysregulated homeostasis, developing lethal lymphoproliferation with multiorgan inflammation. In this study, we show that surprisingly these have an enlarged population Foxp3(+) regulatory T cells (Treg). increase in Treg associated normal thymic output but enhanced proliferation...
CTLA-4 transendocytosis is elicited by self-antigens and down-regulates costimulatory ligands on migratory dendritic cells.