DR5 DataRelease
Release Date: 11/01/2013
| SDY60: Decay of Memory T cells In Old Population | |||||||
| Status: | New | ||||||
| Description: | To expand our study of T cell memory repertoires in an aging population for which the repertoires may be decaying. These studies will provide data about the aging-specific dynamics of memory repertoires. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M38OJI5XI0 | ||||||
| Subjects: | 70 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY110: Immune responses to Helicobacter pylori in a pig model | ||||||||||
| Status: | New | |||||||||
| Description: | We have developed for the first time a pig model to study mucosal and systemic Th1 and CD8+ cytotoxic immune responses to H. pylori infection. | |||||||||
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| DOI: | 10.21430/M3WXZHC81N | |||||||||
| Subjects: | 15 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY148: The Role of Peroxisome Proliferator-Activated Receptor gamma in Immune Responses to Enteroaggregative Escherichia coli Infection | |||||||
| Status: | New | ||||||
| Description: | Background: Enteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood;due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARg) in the modulation of host responses to EAEC in nourished and malnourished mice. Methods/Principal Findings: Wild-type and T cell-specific PPARg null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5x10^9 cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to E. coli antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARg in T cells resulted in upregulation of Tgfb1, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPAR gamma blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 in vivo. Conclusions: Our studies provide in vivo evidence in support of supporting the beneficial role of mucosal innate and effector T cell responses on the EAEC burden and suggest pharmacological blockade of PPARg as a novel therapeutic intervention for EAEC infection. | ||||||
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| DOI: | 10.21430/M36I96JIIZ | ||||||
| Subjects: | 243 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY214: Impact of Nutrition and Nitazoxanide on Enteroaggregative Escherichia coli (EAEC) Infection | |||||||||||||
| Status: | New | ||||||||||||
| Description: | Enteroaggregative Escherichia coli (EAEC) is increasingly recognized as a common cause of diarrhoea in healthy, malnourished and immune-deficient adults and children. There is no reproducible non-neonatal animal model for longitudinal studies of disease mechanism or therapy. Using two strains of human-derived EAEC to challenge weaned C57BL/6 mice, we explored an in vivo model of EAEC infection in mice, in which disease was monitored quantitatively as the growth rate, stool shedding and tissue burden of organisms; nutritional status was varied, and a new class of therapeutics was assessed. A single oral challenge of EAEC strain 042 resulted in significant growth shortfalls (5-8?% of body weight in 12 days), persistent shedding of micro-organisms in stools [>10(3.2) c.f.u. (10 mg stool)(-1) for at least 14 days] and intestinal tissue burden [~10(3) c.f.u. (10 mg tissue)(-1) detectable up to 14 days post-challenge]. Moderate malnourishment of mice using a 'regional basic diet' containing 7?% protein and reduced fat and micronutrients heightened all parameters of infection. Nitazoxanide in subMIC doses, administered for 3 days at the time of EAEC challenge, lessened growth shortfalls (by >10?% of body weight), stool shedding [by 2-3 logs (10 mg stool)(-1)] and tissue burden of organisms (by >75?% in the jejunum and colon). Thus, weaned C57BL/6 mice challenged with EAEC is a convenient, readily inducible model of EAEC infection with three highly quantifiable outcomes in which disease severity is dependent on the nutritional status of the host, and which is modifiable in the presence of inhibitors of pyruvate ferredoxin oxidoreductase such as nitazoxanide. | ||||||||||||
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| DOI: | 10.21430/M3NQ3UF8O9 | ||||||||||||
| Subjects: | 100 | ||||||||||||
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| Assays: | None | ||||||||||||
| Clinical Assessments: | None | ||||||||||||
| SDY216: CD4+ T cell differentiation studies | ||||||||||
| Status: | New | |||||||||
| Description: | Differentiation of CD4+ T cells into effector or regulatory phenotypes is tightly controlled by the cytokine milieu, complex intracellular signaling networks and numerous transcriptional regulators. We combined experimental approaches and computational modeling to investigate the mechanisms controlling differentiation and plasticity of CD4+ T cells in the gut of mice. Our computational model encompasses the major intracellular pathways involved in CD4+ T cell differentiation into T helper 1 (Th1), Th2, Th17 and induced regulatory T cells (iTreg). Our modeling efforts predicted a critical role for peroxisome proliferator-activated receptor gamma (PPARg) in modulating plasticity between Th17 and iTreg cells. PPARg regulates differentiation, activation and cytokine production, thereby controlling the induction of effector and regulatory responses, and is a promising therapeutic target for dysregulated immune responses and inflammation. Our modeling efforts predict that following PPARg activation, Th17 cells undergo phenotype switch and become iTreg cells. This prediction was validated by results of adoptive transfer studies showing an increase of colonic iTreg and a decrease of Th17 cells in the gut mucosa of mice with colitis following pharmacological activation of PPAR?. Deletion of PPARg in CD4+ T cells impaired mucosal iTreg and enhanced colitogenic Th17 responses in mice with CD4+ T cell-induced colitis. Thus, for the first time we provide novel molecular evidence in vivo demonstrating that PPARg in addition to regulating CD4+ T cell differentiation also plays a major role controlling Th17 and iTreg plasticity in the gut mucosa. | |||||||||
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| DOI: | 10.21430/M36YGDV91N | |||||||||
| Subjects: | 91 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY225: Aerosol Inoculation with a Sub-lethal Influenza Virus Leads to Exacerbated Morbidity and Pulmonary Disease Pathogenesis | |||||||||||
| Status: | New | ||||||||||
| Description: | A mouse model has been extensively used to investigate disease intervention approaches and correlates of immunity following influenza virus infection. IN and aerosol routes of inoculation were compared and end-points of immunity and disease pathogenesis were evaluated in mice using mouse-mouseadapted H3N2 A/Aichi/2/68 (x31). | ||||||||||
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| DOI: | 10.21430/M3SE0EVY36 | ||||||||||
| Subjects: | 5 | ||||||||||
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| Clinical Assessments: | None | ||||||||||
| SDY230: Predictive computational modeling of the mucosal immune responses during Helicobacter pylori infection | ||||||||||
| Status: | New | |||||||||
| Description: | T helper (Th) cells play a major role in the modulation of immune responses at the gastric mucosa and lesion formation during Helicobacter pylori infection. The contributions of CD4+ T cell subsets to gastritis development and control of H. pylori colonization are not well understood. We used two computational approaches: ordinary differential equation (ODE)-based and agent-based modeling (ABM) to study the mechanisms underlying cellular immune responses to H. pylori and the influence of CD4+ T cell subsets in initiation, progression and outcome of disease. To calibrate the model, in vivo experimentation was performed by infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell subsets in the stomach and gastric lymph nodes (GLN) on days 0, 7, 14, 30 and 60 post-infection. Our computational model reproduced the dynamic behaviors of effector and regulatory pathways in the gastric lamina propria (LP) in silico. Simulation results show the induction of an initial Th17 response, followed by a dominant Th1 response, and a regulatory response characterized by high levels of mucosal iTreg cells. We also investigated the potential role of peroxisome proliferator-activated receptor ? (PPAR?) activation in the modulation of host responses to H. pylori by using loss-of-function approaches. Specifically, in silico results showed a predominance of Th1 and Th17 cells in the stomach of the cell-specific PPAR? knockout system when compared to the wild-type simulation. Our ABM suggested similar dynamics in the induction of host responses showing analogous T cell distributions to ODE modeling and facilitated tracking lesion formation. In addition, the myeloid cell-specific PPAR? knockout model illustrated increased Th17 differentiation in the gastric LP. These integrated immunoinformatics approaches characterized the induction of mucosal immunoregulatory pathways controlled by PPAR? during H. pylori infection that affect initiation, progression and outcome of disease. | |||||||||
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| DOI: | 10.21430/M37ANCFRHF | |||||||||
| Subjects: | 53 | |||||||||
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| Clinical Assessments: | None | |||||||||
| SDY232: Determinants of human NK cell diversity by mass cytometry | |||||||
| Status: | New | ||||||
| Description: | Natural Killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 35 parameters, including 28 NK cell receptors, on peripheral blood NK cells from five sets of monozygotic twins and twelve unrelated donors of defined HLA and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6,000-30,000 phenotypic populations within an individual and >100,000 phenotypes in this population. Genetics largely determined inhibitory receptor expression, whereas activation receptor expression was heavily environmentally influenced. Therefore, NK cells may maintain self-tolerance through strictly regulated expression of inhibitory receptors, while using adaptable expression patterns of activating and costimulatory receptors to respond to pathogens and tumors. These findings further suggest the possibility that discrete NK cell subpopulations could be harnessed for immunotherapeutic strategies in the settings of infection, reproduction, and transplantation | ||||||
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| DOI: | 10.21430/M3J7Z67HEA | ||||||
| Subjects: | 22 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY196: Responses to Influenza Vaccination in Systemic Lupus Year 1 2005-2006 | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M3ABJS44K6 | ||||||||||||
| Subjects: | 62 | ||||||||||||
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| SDY197: Responses to Influenza Vaccination in Systemic Lupus Year 2 2006-2007 | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M3FD1QTLQQ | ||||||||||||
| Subjects: | 63 | ||||||||||||
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| SDY198: Responses to Influenza Vaccination in Systemic Lupus Year 3 2007-2008 | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M3D393V41D | ||||||||||||
| Subjects: | 74 | ||||||||||||
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| SDY199: Responses to Influenza Vaccination in Systemic Lupus Year 4 2008-2009 | |||||||||||||
| Status: | Updated | ||||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||||
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| DOI: | 10.21430/M39YLN3479 | ||||||||||||
| Subjects: | 69 | ||||||||||||
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| SDY200: Responses to Influenza Vaccination in Systemic Lupus Year 5 2009-2010 | |||||||||||
| Status: | Updated | ||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||
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| DOI: | 10.21430/M3ZR6IH181 | ||||||||||
| Subjects: | 73 | ||||||||||
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| SDY201: Responses to Influenza Vaccination in Systemic Lupus Year 6 2010-2011 | |||||||||||
| Status: | Updated | ||||||||||
| Description: | Influenza is an important pathogen in the United States, with approximately 20,000 deaths per year, mainly among elderly people or those with underlying medical conditions that increase susceptibility to complications from the disease. In addition, considerable morbidity is associated with influenza with a significant impact in productivity in the workplace and home. Influenza has the potential for much more serious consequences as demonstrated by the appearance of four world-wide pandemics in the last century. In principle, serious influenza outbreaks can be prevented by vaccination. However, vaccination is complicated by two features: First, the influenza virus undergoes frequent mutations in the genes encoding the surface proteins hemagglutinin (HA) and neuraminidase (NA), leading to the need to reformulate the vaccine every year. Second, the appearance of the rapidity with which influenza infections can spread. Thus, influenza holds significant potential as a bioterrorism agent. Lupus patients have an increased risk of infection and mount lower responses to vaccinations. The objectives of this study will use genetic, cellular and humoral techniques to identify and explain abnormalities in the immune response to influenza vaccination in lupus patients. The results will clarify vaccine effectiveness among affected patients, increase the understanding of immune dysregulation in lupus, and aid in establishing guidelines for the effective vaccination of lupus patients. The benefits to the subjects are not direct; however, information gained may improve responses of reducing or preventing influenza among the affected population. Additionally, with an increased understanding of the processes of lupus, targets for disease intervention or strategies for treatment may appear. | ||||||||||
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| DOI: | 10.21430/M35J0WA7CR | ||||||||||
| Subjects: | 34 | ||||||||||
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