CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Specimen part, Time
View SamplesMicroarray analysis of gene expression in the olfactory epithelium of macrophage depleted mice to study the role of macrophages in regulating neurodegeneration, neuroprotection, and neurogenesis of olfactory sensory neurons
Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium.
No sample metadata fields
View SamplesData present the expression analysis of different mouse ES cell line with altered expression of GTF2I.
TFII-I regulates target genes in the PI-3K and TGF-β signaling pathways through a novel DNA binding motif.
Specimen part
View SamplesPulmonary dendritic cells are heterogenous cells comprise four distinct subsets including two conventional dendritic cell subsets, CD103+ and CD11bhiCD14lo cells, and two monocyte-derived dendritic cell subsets. Their functions in terms of migration and T cell activation are distinct, but genes regulating their features are to be determined.
Complement receptor C5aR1/CD88 and dipeptidyl peptidase-4/CD26 define distinct hematopoietic lineages of dendritic cells.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor.
Sex, Specimen part
View SamplesRecent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse.
Progression of human bronchioloalveolar carcinoma to invasive adenocarcinoma is modeled in a transgenic mouse model of K-ras-induced lung cancer by loss of the TGF-β type II receptor.
Specimen part
View SamplesConjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit tumorigenesis in a variety of cancer model systems. Based on previously well-documented anti-tumor activity of CLA in rodent models of breast cancer, a pilot study was initiated to examine the effect of dietary CLA in a well-established transgenic model of breast cancer. Western blots were performed for the detection of AKT, c-Src, ERK1/2, and Cdc24. CLA significantly increased tumor burden (p<0.1) independent of an increase in oncogenic signaling. Mammary gland whole mounts indicated a loss of mammary adipose and extensive epithelial expansion in CLA-treated animals. Microarray analysis indicated a significant reduction in cytoskeletal related genes with at least a two-fold decrease in five out of six CLA-fed animals compared to untreated controls. Reduction of Cdc42, a key regulator of cell adhesion and cytoskeletal arrangements, was confirmed at the protein level by western blot (p<0.01). These findings suggest that dietary CLA may advance the malignant phenotype by promoting a loss of cell polarity and adhesion in the mammary gland epithelium. This action may have serious clinical implications for a subset high-risk population and warrants further investigation.
Pilot study on the effects of dietary conjugated linoleic acid on tumorigenesis and gene expression in PyMT transgenic mice.
Sex, Age, Specimen part
View SamplesAs4.1 cells are a renin-expressing cell line commonly used to study the molecular regulation of the mouse renin gene. In the present study, the global gene expression profile was assessed in these cells under control conditions (VEHICLE) and after treatment with interleukin (IL) or hydrogen peroxide (HP), both of which negatively regulate mouse renin gene expression.
Regulation of renin gene expression by oxidative stress.
No sample metadata fields
View SamplesTo examine the role of CREB overexpression in hematopoiesis, we created a model of leukemia in zebrafish by overexpressing the human CREB in the myeloid hematopoietic lineage. Whole transcriptome analysis of kidney-marrow revealed 171 genes differently expressed between CREB- and control-zebrafish (five per group). Interestingly, the integration of this signature with human deposited data revealed that this tumor resembled a human AML at transcriptome level.
CREB engages C/EBPδ to initiate leukemogenesis.
Specimen part
View SamplesDuring embryogenesis, the endothelial and the hematopoietic lineages first appear during gastrulation in the blood island of the yolk sac. We have previously reported that an Ets variant gene 2 (Etv2/ER71) mutant embryo lacks hematopoietic and endothelial lineages, however, the precise roles of Etv2 in yolk sac development remains unclear.
Etv2 is expressed in the yolk sac hematopoietic and endothelial progenitors and regulates Lmo2 gene expression.
Cell line
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