A5046192595- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Blood disorders and treatments
- interferon and immune responses
- Proteoglycans and glycosaminoglycans research
- CAR-T cell therapy research
- Chemokine receptors and signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Protease and Inhibitor Mechanisms
- NF-κB Signaling Pathways
- Hydrology and Watershed Management Studies
- PI3K/AKT/mTOR signaling in cancer
- Redox biology and oxidative stress
- Immune responses and vaccinations
- Sulfur Compounds in Biology
- Tattoo and Body Piercing Complications
- Influenza Virus Research Studies
- Allergic Rhinitis and Sensitization
- Autophagy in Disease and Therapy
- Rheumatoid Arthritis Research and Therapies
- Conservation, Biodiversity, and Resource Management
Babraham Institute
2007-2023
University of Cambridge
2003-2005
University of Saskatchewan
1997
British Society for Rheumatology
1996
Centenary Institute
1995
Bristol Royal Infirmary
1995
Forschungs- und Beratungsstelle Arbeitswelt
1993-1995
University of Oxford
1995
The interaction of interleukin 8 (IL-8) with heparin was studied by using synthetic IL-8 analogs C- and N-terminal truncations. Elimination the region preceding first cysteine, which constitutes receptor binding site, did not affect affinity to heparin-Sepharose. Affinity, however, decreased progressive truncation at C terminus, no observed when C-terminal alpha-helix eliminated. effect other glycosaminoglycans on activity also tested. When applied together heparan sulfate, neutrophil...
Abstract The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity older individuals. A functional GC requires co-ordination multiple cell types across time space, particular its two functionally distinct compartments: light dark zones. In aged mice, there is CXCR4-mediated mislocalization T follicular helper (T FH ) cells to zone a compressed network dendritic (FDCs) zone. Here we show that localization critical for antibody...
Abstract Collagen type II‐induced arthritis (CIA) is an experimental model of that has been successfully used to dissect the pathogenesis human rheumatoid and identify potential therapeutic targets. We have this evaluate role T cell co‐stimulation in both disease development progression. provided by ligation CD28 with either B7‐1 or B7‐2 present on antigen‐presenting cells can be prevented a soluble form CTLA‐4 (CTLA‐4Ig) which binds high affinity B7‐2. found administration CTLA‐4Ig at time...
The generation of high-affinity Abs is essential for immunity and requires collaboration between B T cells within germinal centers (GCs). By using novel mouse models with a conditional deletion the p110δ catalytic subunit PI3K pathway, we established that required in cells, but not GC reaction. We found formation follicular helper (T(FH)) to be critically dependent on cells. Furthermore, by deleting phosphatase tensin homolog deleted chromosome 10, which opposes activated positive...
Abstract The role of PI3K activity in T lymphocyte development is obscure because mice deficient single catalytic subunits either die before birth (p110α−/− and p110β−/−) or lack a significant cell developmental phenotype (p110γ−/− p110δ−/−). We have generated both p110γ p110δ show that p110γ/δ−/− profound block occurs at the β-selection checkpoint. pre-TCR-induced signaling significantly reduced thymocytes this results concomitant proliferative expansion increased apoptosis. survival defect...
Abstract Objective . To characterize the cytokine profile of activated T cell population derived from synovial membrane rheumatoid arthritis (RA) patients. Methods Interleukin‐2 (IL‐2) was used to select for in vivo–activated cells 2 patients with RA, and were cloned nonspecifically. The production these clones compared that peripheral blood monocytes (PBM) by stimulating all 24 hours immobilized anti‐CD3 (coated at 10 μg/ml) or phorbol‐12‐myristate‐13‐acetate (10 ng/ml) plus soluble (1...
Abstract Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity mortality associated with infectious disease older people. We have previously shown that impaired immunity vaccination occurs aged individuals partly attributed effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how intrinsically affects Tfh formation both mice humans. show increased precursors (pre‐Tfh) but no increase germinal centre (GC)‐Tfh cells...
Summary The capacity of the immune system to respond efficiently new antigens depends upon a continuous source naive CD4 + T cells. Such cells exit from thymus and join recirculated T‐cell pool. Factors present at sites circulation must be responsible for their survival, since removal host, die. However, such factors remain unknown. presence cytokine interleukin‐7 (IL‐7) in secondary lymphoid organs expression its receptor on prompted us examine possibility that IL‐7 might survival factor...
An effective immune system depends upon regulation of lymphocyte function and homeostasis. In recent years, members the GTPases immunity associated protein (GIMAP) family were proposed to regulate T cell contrast, little is known about their mode action in B cells. We used a combination transgenic mice vivo vitro techniques conditionally electively ablate GIMAP1 resting activated peripheral Our data suggest that absolutely essential for survival cells, irrespective activation state. Together...
The importance of thyrotropin receptor (TSHR) agonist antibodies in the manifestations Graves' disease (GD) is recognized. There are, however, no convincing reports TSHR-specific T cells. We have previously cloned cells specific for thyroglobulin and thyroid peroxidase (TPO) from GD lymphoid infiltrates used autologous EBV-transformed B cell lines (EBVL) transfected with an expression vector encoding TPO to efficiently detect TPO-specific Here we EBVL TSHR seek infiltrates, after cloning...
Abstract Sweating in humans is induced by physical or emotional stress, which raises the possibility that sweating may relate to host defense. We therefore asked whether human eccrine sweat attracts leukocytes and found it chemotactic for neutrophils. This activity was due several chemoattractants, one of interleukin-8 (IL-8). Using immunohistochemistry situ hybridization IL-8 its mRNA have been detected gland epithelium, indicating produced situ. establishes a pattern physiological...
Abstract RhoG is a Rho family small GTPase implicated in cytoskeletal regulation, acting either upstream of or parallel to Rac1. The precise function(s) vivo has not yet been defined. We have identified novel role for signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor agonists. Bone marrow-derived neutrophils from knockout (RhoG−/−) mice exhibited marked impairment oxidant generation response C5a fMLP, but normal responses PMA opsonized zymosan and bacterial...
An effective immune system depends upon the survival of mature T cells in periphery. Members GIMAP family GTPases have been proposed to regulate this homeostasis, supported by paucity peripheral rodents deficient for either GIMAP1 or GIMAP5. It is unclear whether lack a consequence an ontological defect, causing thymus generate and export incapable surviving periphery, (alternatively additionally) intrinsically require survival. Using ER T2 Cre + transgene, we conditionally deleted Gimap1...
Chemokines are small glycosaminoglycan (GAG) binding proteins that direct the migration of leukocytes by signaling through G protein coupled receptors (GPCR). Many viruses encode disrupt chemokine responses. The murine gammaherpesvirus-68 gene M3 encodes a (vCKBP-3), which has no sequence similarity to receptors. Initial characterization vCKBP-3 showed it inhibits receptor and chemokine-induced calcium influx. structural requirements for chemokines CXCL8 CCL2 bind have been determined. Both...
Interleukin (IL)-4 is considered to be essential for T helper (Th)2 cell development, yet in areas of primary activation, CD4+ cells are its only source. This implies that other signals must drive the initial expression IL-4 production. The role CD28 co-stimulation Th2 subset development has been described. However, mice deficient CD28, responses diminished, but not abrogated. Cytokines produced within lymphoid tissue, e.g. IL-7, may important activation naive cells. We have found human...
SUMMARY Sjögren’s syndrome (SS) is characterized by a focal periductal salivary gland infiltrate consisting mainly of T and B lymphocytes. Most the cells bear memory CD4+ Th-1-like phenotype express high levels class II, though CD8+ are also present. We have studied 17 labial 15 peripheral blood cell clones from patient with primary SS. The tissue were 71% 29% CD4+, blood-derived 60% 40% CD4+. both autologous Th1 phenotype, in that they produced interferon-gamma (IFN-γ) IL-2 but very little...
ABSTRACT Viruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus 68 gene M3 encodes a binding protein (vCKBP-3) which has no sequence similarity to receptors but inhibits receptor and activity. We have used panel of CXCL8 analogs identify the structural requirements for bind vCKBP-3 in scintillation proximity assay. Our data suggest acts by mimicking CXCL8.
Background GTPases of the immunity-associated protein family (GIMAPs) are predominantly expressed in mature lymphocytes. Studies rodents deficient GIMAP1, GIMAP4, or GIMAP5 have demonstrated that these regulate lymphocyte survival. In contrast to other members, GIMAP8 contains three potential GTP-binding domains (G-domains), a highly unusual feature suggesting novel function for this protein. To examine role biology we examined expression during development. We also generated mouse and...