A5015295914- Hepatitis B Virus Studies
- Hepatitis C virus research
- Liver Disease Diagnosis and Treatment
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Hepatitis Viruses Studies and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- COVID-19 Clinical Research Studies
- Diabetes and associated disorders
- SARS-CoV-2 detection and testing
- Viral Infections and Outbreaks Research
- Extracellular vesicles in disease
- Viral gastroenteritis research and epidemiology
- Liver Diseases and Immunity
- Immune responses and vaccinations
- Vaccine Coverage and Hesitancy
- Intensive Care Unit Cognitive Disorders
- Immune Response and Inflammation
- HIV-related health complications and treatments
- Monoclonal and Polyclonal Antibodies Research
- Taxation and Compliance Studies
- S100 Proteins and Annexins
- Phagocytosis and Immune Regulation
Queen Mary University of London
2016-2025
La Jolla Institute for Immunology
2024
The University of Melbourne
2024
Barts Health NHS Trust
2013-2023
National Bureau of Economic Research
2019-2023
Chelsea and Westminster Hospital NHS Foundation Trust
2023
Royal Free London NHS Foundation Trust
2023
Government of the United Kingdom
2023
United States Congress
2023
Royal London Hospital
2010-2022
Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates hepatocytes but is non-cytopathic; liver damage thought to be immune mediated. Here, we investigated the role of innate responses mediating patients with HBV infection. Longitudinal analysis revealed a temporal correlation between flares inflammation and fluctuations interleukin (IL)-8, interferon (IFN)-α, natural killer (NK) cell expression tumor necrosis factor–related...
A regulatory subset of B cells has been found to modulate immune responses in autoimmunity, infection, and cancer, but it not investigated the setting human persistent viral infection. IL-10 is elevated patients with chronic hepatitis virus infection (CHB), its cellular sources impact on antiviral T have addressed. We role pathogenesis CHB. Serum levels were studied longitudinally CHB undergoing spontaneous disease flares. There was a close temporal correlation between fluctuations load or...
Antiviral T cell responses in hepatotropic viral infections such as hepatitis B virus (HBV) are profoundly diminished and prone to apoptotic deletion. In this study, we investigate whether the large population of activated NK cells human liver contributes process. We show that vitro removal augments circulating CD8+ directed against HBV, but not well-controlled viruses, patients with chronic (CHB). find can rapidly eliminate HBV-specific a contact-dependent manner. microcirculation...
Abstract An excess of coinhibitory signals has been proposed to drive the T-cell exhaustion characteristic persistent viral infections. In this study we examined contribution receptor cytotoxic T lymphocyte antigen-4 (CTLA-4) CD8 cell tolerance in chronic hepatitis B virus (HBV) infection (CHB). cells patients with CHB have an increased propensity express CTLA-4 and correlates load. is up-regulated on those HBV-specific highest levels proapoptotic protein Bim, which previously shown mediates...
The liver provides a tolerogenic immune niche exploited by several highly prevalent pathogens as well primary and metastatic tumors. We have sampled healthy hepatitis B virus (HBV)-infected human livers to probe for subset of T cells specialized overcome local constraints mediate immunity. characterize population T-betloEomesloBlimp-1hiHobitlo found within the intrahepatic but not circulating memory CD8 cell pool expressing liver-homing/retention markers (CD69+CD103+ CXCR6+CXCR3+). These...
B cells are increasingly recognized as playing an important role in the ongoing control of hepatitis virus (HBV). The development antibodies against viral surface antigen (HBV [HBsAgs]) constitutes hallmark resolution acute infection and is a therapeutic goal for functional cure chronic HBV (CHB). We characterized directly ex vivo from blood liver patients with CHB to investigate constraints on their antiviral potential. Unexpectedly, we found that HBsAg-specific persisted many were enriched...
The S-type lectin galectin-9 binds to the negative regulatory molecule Tim-3 on T cells and induces their apoptotic deletion or functional inactivation. We investigated whether galectin-9/Tim-3 interactions contribute exhaustion of antiviral cell response in chronic hepatitis B virus infection (CHB). found be expressed a higher percentage CD4 CD8 from patients with CHB than healthy controls (p<0.0001) enriched activated those infiltrating HBV-infected liver. Direct ex vivo examination...
Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as "baits" for specific ex vivo detection of HBsAg-specific cells and analysis their quantity, function, phenotype. We studied healthy vaccinated subjects (n = 18) patients resolved 21), acute 11), or chronic 96) observed frequencies...
The ability of innate immune cells to sense and respond impending danger varies by anatomical location. liver is considered tolerogenic but still capable mounting a successful response clear various infections. To understand whether hepatic tune their different infectious challenges, we probed mononuclear purified from human healthy diseased livers with distinct pathogen-associated molecules. We discovered that only the TLR8 agonist ssRNA40 selectively activated liver-resident produce...
Abstract Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly healthy diseased liver compared to blood (p < 0.0001). Human hepatic had an immature phenotype (predominantly CD56 bright CD16−CD57−), expressed tissue-residency marker CD69. produced fewer cytotoxic mediators pro-inflammatory cytokines than...
The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, discontinuation associated with and biochemical relapse and, consequently, the majority life-long.
The inflamed liver in chronic hepatitis B virus (HBV) infection (CHB) is characterized by a large influx of non–virus-specific CD8 T cells. Little known about the functional capacity these lymphocytes, which could provide insights into mechanisms failure viral control and damage this setting. We compared effector function total circulating intrahepatic cells CHB patients healthy donors. demonstrated that from patients, regardless their antigen specificity, were impaired ability to produce...
NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated that they upregulate death ligand TRAIL patients with chronic hepatitis B virus infection (CHB), allowing them to kill hepatocytes bearing receptors. In this study we investigated whether, addition their pathogenic role, antiviral potential CHB. characterised cell subsets and effector function 64 CHB compared 31 healthy controls. found that, contrast upregulated...
ABSTRACT CD4 + CD25 regulatory T cells have been shown to maintain peripheral tolerance against self and foreign antigens. In this study we analyzed the effect of circulating on CD8 -T-cell responses patients with chronic resolved hepatitis B virus (HBV) infection. We demonstrated that modulate function expansion HBV-specific ex vivo in all patients, regardless whether they or HBV The possible role pathogenesis infection is not supported by these data. However, results might implications for...
Novices often are reminded of earlier examples during problem solving. Four experiments examine the hypothesis that use promotes generalizations about types, thereby influencing what is learned domain. Subjects studied four probability principles with word problems and then tried to solve two tests for each principle. For half first tests, cues indicated which study might be used. All second were uncued. Discussion focuses on distinction how comparisons used in learning implications view...
Optimal immune activation of naïve CD8 T cells requires signal 1 mediated by the cell receptor, 2 co-stimulation and 3 provided pro-inflammatory cytokines. However, potential for cytokines to rescue anti-viral responses in functionally exhausted has not been defined. We investigated effect using third IL-12 or IFN-α response characteristic patients persistently infected with hepatitis B virus (HBV). found that IL-12, but IFN-α, potently augmented capacity HBV-specific produce effector upon...
Liver involvement in sarcoidosis is variable and can occur the absence of pulmonary disease. Data on natural history hepatic sarcoid response to therapy are lacking. This study investigates dysfunction complicating lung disease significant liver presenting independent sarcoid.One hundred eighty patients were included study. The minimum follow-up was 2 years.Fifty per cent population had derangement function attributable sarcoid. Twenty-three (13%) without Sixty-three administered...