Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA271035 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses. To investigate the mechanism of rescue we performed RNA microarray analyses to identify whether there was a genetic “signature” of rescue. mRNA was obtained from whole spleens 6 hrs after revaccination with LM-DActA at D1 and D4 PI for RNA microarray analysis
2015-09-01 | E-GEOD-64434 | biostudies-arrayexpress
Project description:In two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses.
2015-09-01 | GSE64434 | GEO
Project description:Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses. Total RNA was extracted from sorted memory CD8 T cells induce by CMV and adenoviral vectors, and naïve CD8 cells
2015-09-23 | E-GEOD-73314 | biostudies-arrayexpress
Project description:Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.
2015-09-23 | GSE73314 | GEO
Project description:Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection. However, despite heightened readiness to respond, memory cells exist in a functionally quiescent state. The paradigm is that memory cells remain inactive due to lack of TCR stimuli. Here we report a unique role of Tregs in orchestrating memory quiescence by inhibiting effector and proliferation programs through CTLA-4. Loss of Tregs resulted in activation of genome-wide transcriptional programs characteristic of potent effectors, and both developing and established memory quickly reverted to a terminally differentiated (KLRG-1hi/IL-7R±lo/GzmBhi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality and protective efficacy. CTLA-4, an inhibitory receptor overexpressed on Tregs, functionally replaced Tregs in trans to rescue Treg-less memory defects and restore homeostasis of secondary mediators as well. These studies present CD28-CTLA-4-CD80/CD86 axis as a novel target to potentially accelerate vaccine-induced immunity and improve T-cell memory quality in current cancer immunotherapies proposing transient Treg-depletion. We used microarray analysis to detail the global programming of gene expression in LCMV GP33-specific CD8 T cells differentiated in the presence or absence of regulatory T cells Differentiation of memory CD8 T cells entails a progressive transition of highly activated effector program to a quiescent memory program. A key question in the field is to understand the factors that aid in the differentiation of memory cells from effector cells. It is a generally accepted paradigm that effector cells transition to a memory state by default after antigen clearance, since TCR stimuli is the key driver of effector programs in CD8 T cells. We hypothesized that the effector to memory transition of CD8 T cells involves active immunological brakes through regulatory T cells (Tregs) that allow the highly activated effector cells to convert into quiescent memory cells. To address this hypothesis, we used FoxP3-DTR mice to deplete Tregs during the window following antigen clearance, during which the effector CD8 T cells convert to long-lived memory cells. To get a deeper understanding of the global transcriptome of CD8 T cells as they transition from an effector to a memory state, we isolated and arrayed the antigen-specific CD8 T cells at day 16 post-infection that have experienced the transitional environment with and without the presence of Tregs.
2015-06-16 | E-GEOD-67593 | biostudies-arrayexpress
Project description:CD8 T cells play a crucial role in immunity to infection and cancer. They are maintained in constant numbers, but upon stimulation with antigen undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific populations, followed by the persistence of long-lived memory cells. Although this predictable pattern of a CD8 T cell response is well established, the underlying cellular mechanisms regulating the transition to memory remain undefined. Here we show that TRAF6, an adapter protein in the TNF-receptor (TNFR) and IL-1R/TLR superfamily, regulates CD8 T cell memory development following infection by modulating fatty acid metabolism. We show that mice with a T cell-specific deletion of TRAF6 mount robust primary CD8 T cell effector responses, but have a profound defect in their ability to generate memory. This defect is CD8 T cell intrinsic and is characterized by the disappearance of antigen-specific cells in the weeks following primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells from early timepoints following immunization exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 are unable to upregulate mitochondrial β-oxidation in response to growth factor withdrawal in vitro. Treatment with drugs that induce fatty acid oxidation enabled CD8 T cell memory generation in the absence of TRAF6. Remarkably, these treatments also increased CD8 T cell memory in wild type mice, and consequently were able to significantly improve the efficacy of an experimental anti-cancer vaccine. Experiment Overall Design: CD8 T cells from two mouse strains (OTI-WT and OTI-TRAF6 knockout) at two timepoints (6d with 3 replicates and 10d with 5 replicates) after infection are used.
2009-06-24 | E-GEOD-15750 | biostudies-arrayexpress
Project description:Increased use of nuclear reactors and radioactive materials for energy production and proliferation of nuclear weaponry increases risk of radiation exposure or nuclear accidents. Development of radiation countermeasures for the diagnosis, prognosis, and radiation treatment are trailing behind, and knowledge of the deleterious radiation effects on health and responses to exposure at the molecular, cellular, and systems biology level are still not fully understood. In this work, skin biopsies collected at h2, d4, d7, d21, and d28 from mice exposed to 1, 3, 6, 20Gy of whole-body x-ray ionizing radiation were used in a transcriptomic approach to evaluate the potential of radiation-induced transcriptional alterations in diagnosis and prognosis of a radiation event. Mice exposed to 20Gy were euthanized under the humane endpoint of an IACUC approved study protocol at d7 while mice that received 1, 3, 6Gy survived the full 28 days time course. Sammon plot analysis showed a clear separation of samples based on survival and timepoints within lethal (20Gy) and in the sublethal (1, 3, 6Gy) IR doses. Differences in the numbers, regulation mode, and fold change of significantly differentially transcribed genes (SDTGs, p < 0.05 and FC > 2) were identified between lethal and sublethal doses. Down and upregulation dominated transcriptomes during the first post-exposure week, respectively. Numbers of SDTGs and percentages of upregulated SDTGs revealed stationary transcription and low upregulation percentages after lethal dose in contrary to transcription responses that were dynamic and largely upregulated after exposure to sublethal doses. Longitudinal variations in numbers of up/downregulated SDTGs suggested delayed and extended responses with increasing IR doses in the sublethal range with lethal-like responses in late time points suggesting more than a single-phase response. This was supported further by the distributions of common and unique genes across the TPs within each dose. Several genes with potential use as markers for radiation exposure and dosimetric applications were identified. Pathways enrichment analysis showed strong modulations of immune responses, fibrosis development, detoxification responses, hematological responses, skin reactions, neurological system disruptions, maintenance of gastric mucosa, and cell survival, migration, and proliferation pathways. The majority of the identified pathways were predicted activated after sublethal and inactivated after lethal exposures, particularly during the first post-exposure week.
2022-03-15 | GSE185149 | GEO
Project description:The generation of CD8+ T-cell memory is an important aim of immunization. While several distinct subsets of CD8+ T-cell memory have been described, the lineage relationships between effector (EFF), effector memory (EM) and central memory (CM) T cells remain contentious. Specifically, there is contradictory experimental evidence to support both the linear (Naive>EFF>EM>CM) and progressive differentiation (Naive>CM>EM>EFF) models. In this study, we applied a systems biology approach to examine global transcriptional relationships between the three major CD8+ T cell subsets arising endogenously as a result of vaccination with three different prime-boost vaccine regimens. Differential gene expression analysis and principle component analysis revealed that central memory cells were more closely related to naive T cells than both effector memory and effector cells. When the transcriptional relationships between subsets were enriched in an unbiased fashion with known global transcriptional changes that result when T-cells repeatedly encounter antigen, our analysis favored a model whereby cumulative antigenic stimulation drives differentiation specifically from Naive > CM > EM > EFF. These findings provide an insight into the lineage relationship between mature CD8+ T-cell subsets and will help in the rational design of vaccines aimed at generating effective immune responses against infections and cancer. Effector (EFF), effector memory (EM), central memory (CM) and naive CD8+ T cells from mice spleen. Memory subset arise endogenously as a result of vaccination with three different prime-boost vaccine regimens: DNA-rAd5, rAd5-rAd5 and rAd5-rLCMV.
2013-08-01 | E-GEOD-42459 | biostudies-arrayexpress
Project description:HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in all vaccinated macaques following high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure.
2021-05-24 | GSE171783 | GEO
Project description:CD8 T cells play a crucial role in immunity to infection and cancer. They are maintained in constant numbers, but upon stimulation with antigen undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific populations, followed by the persistence of long-lived memory cells. Although this predictable pattern of a CD8 T cell response is well established, the underlying cellular mechanisms regulating the transition to memory remain undefined. Here we show that TRAF6, an adapter protein in the TNF-receptor (TNFR) and IL-1R/TLR superfamily, regulates CD8 T cell memory development following infection by modulating fatty acid metabolism. We show that mice with a T cell-specific deletion of TRAF6 mount robust primary CD8 T cell effector responses, but have a profound defect in their ability to generate memory. This defect is CD8 T cell intrinsic and is characterized by the disappearance of antigen-specific cells in the weeks following primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells from early timepoints following immunization exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 are unable to upregulate mitochondrial β-oxidation in response to growth factor withdrawal in vitro. Treatment with drugs that induce fatty acid oxidation enabled CD8 T cell memory generation in the absence of TRAF6. Remarkably, these treatments also increased CD8 T cell memory in wild type mice, and consequently were able to significantly improve the efficacy of an experimental anti-cancer vaccine.
2009-06-05 | GSE15750 | GEO