A5071645696- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hepatitis Viruses Studies and Epidemiology
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- Hepatitis B Virus Studies
- Immune Response and Inflammation
- interferon and immune responses
- Viral Infections and Immunology Research
- Viral Infections and Outbreaks Research
- Inflammasome and immune disorders
- Herpesvirus Infections and Treatments
- Genetic Mapping and Diversity in Plants and Animals
- Molecular Biology Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Genetic and phenotypic traits in livestock
- Adipokines, Inflammation, and Metabolic Diseases
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Viral gastroenteritis research and epidemiology
- Immune responses and vaccinations
- Dermatology and Skin Diseases
- Influenza Virus Research Studies
- Viral Infections and Vectors
University of North Carolina at Chapel Hill
2016-2025
University of North Carolina Health Care
2015-2024
UNC Lineberger Comprehensive Cancer Center
2015-2023
Pediatrics and Genetics
2016-2020
Indiana University School of Medicine
2013-2014
Scripps Research Institute
2004-2009
Emory University
1996-2005
University of California, Los Angeles
2001-2005
AIDS Research Alliance
2004
Oregon Health & Science University
2004
Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the integrity laboratory stocks. We have developed third generation Mouse Universal Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array house mouse (Mus musculus). The bulk content GigaMUGA is optimized mapping in Collaborative Cross Diversity Outbred populations, substrain-level identification mice. In addition to 141,090 single nucleotide polymorphism probes,...
Interferon-γ (IFNγ) is important in regulating the adaptive immune response, and most current evidence suggests that it exerts a negative (proapoptotic) effect on CD8+ T cell responses. We have developed novel technique of dual adoptive transfer, which allowed us to precisely compare, normal mice, vivo antiviral responses two populations differ only their expression IFNγ receptor. use this show that, contrary expectations, strongly stimulates development during an acute viral infection. The...
4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with ligand (4-1BBL) APCs. To investigate the role of costimulation for development primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- able to generate CTL eliminate acute LCMV infection normal kinetics, but CD8 cell expansion was 2- 3-fold lower than in wild-type (+/+) mice. In same mice, virus-specific CD4 Th B responses...
Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of expanded cells undergo apoptosis, leaving behind stable number memory cells. The relationship between clear acute infection and long-lived pool remaining individual is not fully understood. To address this issue, we examined receptor (TCR) repertoire virus-specific mouse model with lymphocytic choriomeningitis virus (LCMV) using three approaches:...
ABSTRACT Cytotoxic T cells secrete perforin to kill virus-infected cells. In this study we show that also plays a role in immune regulation. Perforin-deficient (perf −/−) mice chronically infected with lymphocytic choriomeningitis virus (LCMV) contained greater numbers of antiviral compared persistently +/+ mice. The enhanced expansion was seen both CD4 and CD8 cells, but the most striking difference LCMV-specific present perf −/− Persistent LCMV infection results deletion anergy...
Abstract Although the role of CD28-B7 interaction in activation naive T cells is well established, its importance generation and maintenance cell memory not understood. In this study, we examined requirement for interactions primary immune memory. Ag-specific CD8 responses were compared between wild-type (+/+) CD28-deficient (CD28−/−) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). During response, there was a substantial expansion LCMV-specific both +/+...
B cells can influence T cell responses by directly presenting Ag or secreting Ab that binds to form immunogenic complexes. Conflicting evidence suggests persisting Ag-Ab complexes propagate long-term memory; yet, other data indicate memory survive without specific MHC. In this study, the roles of and in lymphocytic choriomeningitis virus (LCMV) infection were investigated using cell-deficient cell-competent mice. Despite normal lymphocyte expansion after acute infection, mice rapidly lost...
Obesity in humans is associated with poorer health outcomes after infections compared non-obese individuals. Here, we examined the effects of white adipose tissue and obesity on T cell responses to viral infection mice. We show that lymphocytic choriomeningitis virus (LCMV) grows high titer tissue. Virus-specific cells enter resolve but then remain as a memory population distinct from lymphoid tissues. Memory are abundant lean mice, diet-induced further increases number spleen. Upon...
Abstract NK cells have well-established functions in immune defense against virus infections and cancer through their cytolytic activity production of cytokines. In this study, we examined the frequency influence on T cell responses mice given variants lymphocytic choriomeningitis that cause acute or persisting infection. We found increased frequencies circulating during disseminating infection compared with uninfected acutely infected mice. Consistent recent reports, observed depletion...
Hepatotropic viruses are important causes of human disease, but the intrahepatic immune response to hepatitis is poorly understood because a lack tractable small- animal models. We describe murine model A virus (HAV) infection that recapitulates critical features type in humans. demonstrate capacity HAV evade MAVS-mediated I interferon responses defines its host species range. HAV-induced liver injury was associated with interferon-independent intrinsic hepatocellular apoptosis and hepatic...
The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and ability precisely manipulate genome. Despite importance genetics quality control (QC) not standardized, lack cost-effective, informative, robust platforms. Genotyping arrays are standard tools research remain an attractive alternative even era high-throughput whole-genome sequencing. Here, we describe content performance a new iteration...
Abstract CD4 T cells are known to assist the CD8 cell response by activating APC via CD40-CD40 ligand (L) interactions. However, recent data have shown that bacterial products can directly activate through Toll-like receptors, resulting in up-regulation of costimulatory molecules necessary for efficient priming naive cells. It remains unclear what role help and various costimulation pathways play development responses during infection. In this study, we examined these questions using an...
CD40 ligand is expressed on activated T cells and interacts with B monocytes. It not known what role plays in the generation of immune responses to viral infection. To address this issue, we examined virus-specific T- B-cell ligand-deficient (CD40L-/-) mice following infection lymphocytic choriomeningitis virus (LCMV). We found that primary anti-LCMV specific antibody were severely impaired CD40L-/- mice, defect being most striking for immunoglobulin G1 (IgG1) isotype. Interestingly, low...
Abstract This study documents a striking dichotomy between CD4 and CD8 T cells in terms of their requirements for CD40-CD40 ligand (CD40L) costimulation. CD40L-deficient (−/−) mice made potent virus-specific cell responses to dominant as well subdominant epitopes following infection with lymphocytic choriomeningitis virus. In contrast, the very same mice, were severely compromised. There 10-fold fewer CD40L−/− compared those CD40L+/+ this inhibition was seen both Th1 (IFN-γ, IL-2) Th2 (IL-4)...
Abstract Peptide vaccination induces T cell activation and cytotoxic development. In an effort to understand what factors can improve immune responses peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since has been shown promote in other systems. 4-1BBL-deficient (−/−) wild-type (+/+) mice were immunized with a lipidated lymphocytic choriomeningitis virus (LCMV) NP396–404. Analysis peptide-specific early after immunization by CTL assay, intracellular IFN-γ staining,...
We found that mice infected with different isolates of lymphocytic choriomeningitis virus (LCMV) develop a mild hemorrhagic anemia, which becomes severe and eventually lethal in animals depleted platelets or lacking integrin β3. Lethal anemia is mediated by virus-induced IFN-α/β causes platelet dysfunction, mucocutaneous blood loss suppression erythropoiesis. In addition to the life-threatening platelet-depleted fail mount an efficient cytotoxic T lymphocyte (CTL) response cannot clear LCMV....
Intracellular cytokine detection by flow cytometry has emerged as the premier technique for studying production at single-cell level. Multiparameter permits simultaneous of two or more cytokines within a single cell, allowing direct T(H)1 versus T(H)2 determination. This capability, combined with high throughput inherent in instrumentation, gives intracellular staining an enormous advantage over existing techniques such ELISPOT, limiting dilution, and T cell cloning. The unit describes cells...