A5004145352- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Oral Health Pathology and Treatment
- Skin Diseases and Diabetes
- Surgical Sutures and Adhesives
- Lung Cancer Research Studies
- Cancer Diagnosis and Treatment
- Autoimmune and Inflammatory Disorders
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Immune cells in cancer
- Gene Regulatory Network Analysis
- Monoclonal and Polyclonal Antibodies Research
- Oral and gingival health research
- Information Systems Education and Curriculum Development
University College London
2020-2025
The Royal Free Hospital
2020-2025
Institute of Infection and Immunity
2025
Brigham Young University
2019
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....
CD80 and CD86 are expressed on antigen presenting cells required to engage their shared receptor, CD28, for the costimulation of CD4 T cells. It is unclear why two stimulatory ligands with overlapping roles have evolved. also bind regulatory molecule CTLA-4. We explored role in homeostasis proliferation CD4+FoxP3+ (Treg), which constitutively express high levels CTLA-4 yet critically dependent upon CD28 signals. observed that was dominant ligand Treg proliferation, survival, maintenance a...
Abstract CTLA‐4 and PD‐1 are key immune checkpoint receptors that targeted in the treatment of cancer. A recently identified physical interaction between respective ligands, CD80 PD‐L1, has been shown to block PD‐L1/PD‐1 binding prevent PD‐L1 inhibitory functions. Since is known capture degrade its ligands via transendocytosis, we investigated interplay transendocytosis CD80/PD‐L1 interaction. We find results a time‐dependent recovery availability correlates with removal. Moreover, highly...
Heterozygous mutations in CTLA-4 result an inborn error of immunity with autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications allogeneic hematopoietic stem transplantation. Here, we designed homology-directed repair (HDR) editing strategy that inserts cDNA into first intron genomic locus primary human cells. This resulted regulated expression CD4 + cells, functional studies demonstrated CD80 CD86...
Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying determinants of duration immunity. The quality persistence circulating CD4 effector (TEM) central (TCM) cells in mice appear to shift age, but it unclear whether these changes driven by aging host environment, age effects, or both. Here, we address issues combining DNA labelling methods, established fate-mapping systems, a novel reporter mouse strain, mathematical models....
Tissue-resident memory T cells (T RM ) protect from repeated infections within organs and barrier sites. The breadth duration of such protection is defined at minimum by three quantities; the rate which new are generated precursors, their self-renewal, loss through death, egress, or differentiation. Quantifying these processes in isolation challenging. Here we combine genetic fate mapping tools mathematical models to untangle basic homeostatic properties CD4 + skin lamina propria (LP)...
Tissue-resident memory T cells (T RM ) protect from repeated infections within organs and barrier sites. The breadth duration of such protection is defined at minimum by three quantities; the rate which new are generated precursors, their self-renewal, loss through death, egress, or differentiation. Quantifying these processes in isolation challenging. Here we combine genetic fate mapping tools mathematical models to untangle basic homeostatic properties CD4 + skin lamina propria (LP)...
CD80 and CD86 are expressed on antigen presenting cells (APCs) their role in providing costimulation to T is well established. However, it has been shown that these molecules can also be by cells, but the significance of this observation remains unknown. We have investigated stimuli control expression show APC-free conditions around 40% activated, proliferating CD4+ express either CD80, or both. Expression was strongly dependent upon provision CD28 as ligands were not following TCR...
CTLA-4 is an essential regulator of T-cell immune responses whose intracellular trafficking a hallmark its expression. Defects in due to LRBA deficiency cause profound autoimmunity humans. rapidly internalizes via clathrin-dependent pathway followed by poorly characterized recycling and degradation fates. Here, we explore the impact manipulating Rab GTPases on expression determine how these proteins affect trafficking. We observe that distributed across several compartments marked Rab5, Rab7...
We now come to the consideration of diseases alimentary canal, beginning with inflammation ; and perhaps it will be better com- mence intense forms inflammation, previous considering functional diseases.As varieties they are distin- guished by rules which we have already laid down, when treating inflammations air-tubes, same divisions phenomena may here made: that is say, superficial deep-seated.This distinction was made Cullen, who divided gastritis into erythcmatica or superficial,...
Abstract T-cell activation is a critical driver of immune responses. The CD28 costimulation an essential regulator CD4 responses, however, its relative importance in naive and memory T cells not fully understood. Using different model systems, we observe that human are more sensitive to than cells. To deconvolute how the receptor (TCR) orchestrate cells, stimulate using varying intensities TCR profiled gene expression. We show genes involved cell cycle progression division CD28-driven but...
The dynamics of cell populations are frequently studied in vivo using pulse-chase DNA labeling techniques. When combined with mathematical models, the kinetic label uptake and loss within a population interest then allows one to estimate rates production turnover through death or onward differentiation. Here we explore an alternative method quantifying cellular dynamics, fate-mapping mouse model which dividing cells can be induced constitutively express fluorescent protein, Ki67 reporter...
Having gone through the diseases of chest, we proceed now to con- sider those alimentary canal, beginning with mouth and fauces.The lining membrane fauces is very liable inflammation, may divide inflammation attacking these parts, like that air-tubes respiratory apparatus, into superficial deep-seated.The accompanied by some amount redness-some change in state secretion ; first all, perhaps, there a deficiency secretion, feeling soreness part afterwards an undue attended, perhaps irritation...
Tissue-resident memory T cells (T
SIGITE 2012 included a report1 of Information Technology (IT) bachelor's degree programs in the USA as compared to IT2008 Model Curriculum2. New IT curriculum guidelines were released by ACM late 20173. This paper describes process for identifying and evaluating United States per new 2017 guidelines. Due widespread variation names academic programs, one cannot simply count those named "Information Technology." research, funded SIGITE, first defined framework compliance an program standard...
Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, mechanism by which anti-CTLA-4 work is still controversial. Two major checkpoint (ipilimumab and tremelimumab) been trialled clinically. Both high affinity binding to CTLA-4 occupy ligand site, however recently it has suggested that in some settings such may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities these a variety using both soluble...
Quantifying the kinetics with which memory T cell populations are generated and maintained is essential for identifying determinants of duration immunity. The quality persistence circulating CD4
Abstract CTLA-4 and PD-1 are key immune checkpoints that targeted in the treatment of cancer. Recently it has emerged there is a physical interaction between ligands these pathways (CD80 PD-L1), which can prevent PD-L1 inhibitory functions. Since captures degrades its via transendocytosis, we investigated how transendocytosis CD80 impacted by interaction. We find results time-dependent recovery availability correlates with removal. Moreover, highly specific only removed, heterodimeric...