Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA100293 | ENA |
REPOSITORIES: ENA
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Project description:There remains a need for analysis of CD4 helper T cells differentiation in vivo. To this end ovalbumin (OVA)-specific CD4 (OTII) T cells transferred into congenic mice were studied. Live attenuated OVA-expressing Salmonella (SalOVA) induce T-bet and IFN-g in OTII cells, while alum-precipitated OVA (alumOVA) induces GATA-3 and IL-4. Although 70% of alumOVA-responding OTII cells express GATA-3, only 7% produce IL-4. Thus Th2-polarization defined solely by IL-4 production does not recognize the diversity of GATA-3-expressing effectors. Low-density arrays were designed to assess the expression of 384 genes by real-time RT-PCR. Extensive early diversification occurred in both responses. SalOVA selectively induced many chemokines and pro-inflammatory cytokines, while alumOVA induced few Th2-associated cytokines. Several cytokines and molecules associated with Th17 cells and follicular helper cells were also induced by both antigens. The transcription factor Helios was exclusively induced in alumOVA-responding OTII cells, and critically not in standard in vitro Th2-polarization systems. Early synchronous up-regulation of Helios and GATA-3 mRNA is paralleled at protein level with largely coincident localization in specific nuclear foci of OTII cells responding to alumOVA. This appears to be consistent with a key role for both transcription regulators in the direction of Th2 responses in vivo. Keywords: In vivo T cell polarization Ovalbumin (OVA)-specific CD4 (OTII) T cells were transferred into C57BL/6 mice that were immunized either with live attenuated OVA-expressing Salmonella (Sal) or with alum-precipitated OVA (alum), or not (Naïve). Gene expression assay was performed on FACS sorted OTII cells (Naïve, Sal, Alum). OTII cells were purified from three independent groups of ten naïve, or SalOVA-immunized or alumOVA-immunized mice.
2008-06-27 | E-GEOD-7481 | biostudies-arrayexpress
Project description:There remains a need for analysis of CD4 helper T cells differentiation in vivo. To this end ovalbumin (OVA)-specific CD4 (OTII) T cells transferred into congenic mice were studied. Live attenuated OVA-expressing Salmonella (SalOVA) induce T-bet and IFN-g in OTII cells, while alum-precipitated OVA (alumOVA) induces GATA-3 and IL-4. Although 70% of alumOVA-responding OTII cells express GATA-3, only 7% produce IL-4. Thus Th2-polarization defined solely by IL-4 production does not recognize the diversity of GATA-3-expressing effectors. Low-density arrays were designed to assess the expression of 384 genes by real-time RT-PCR. Extensive early diversification occurred in both responses. SalOVA selectively induced many chemokines and pro-inflammatory cytokines, while alumOVA induced few Th2-associated cytokines. Several cytokines and molecules associated with Th17 cells and follicular helper cells were also induced by both antigens. The transcription factor Helios was exclusively induced in alumOVA-responding OTII cells, and critically not in standard in vitro Th2-polarization systems. Early synchronous up-regulation of Helios and GATA-3 mRNA is paralleled at protein level with largely coincident localization in specific nuclear foci of OTII cells responding to alumOVA. This appears to be consistent with a key role for both transcription regulators in the direction of Th2 responses in vivo. Keywords: In vivo T cell polarization
2008-06-27 | GSE7481 | GEO
Project description:Chicken ovalbumin (cOVA) has been studied for decades primarily due to the robust genetic and molecular resources that are available for experimental investigations. cOVA is a member of the serpin superfamily of proteins that function as protease inhibitors, although cOVA does not exhibit this activity. As a serpin, cOVA possesses a protease-sensitive reactive-center loop that lies adjacent to the OVA 323-339 CD4+ T-cell epitope. We took advantage of the previously described single-substitution-variant, OVA R339T, which can undergo the dramatic structural transition observed in serpins to study how changes in loop size and protein stability influences CD4+ T-cell priming in vivo. We observed that the OVA R339T loop-insertion increases stability and protease resistance, resulting in reduced CD4+ T-cell priming of the OVA 323-339 epitope in SJL mice. These findings have implications for the design of more effective vaccines for the treatment of infectious diseases and cancer as well as the development of more robust CD4+ T-cell-epitope prediction tools.
2021-05-07 | PXD021756 | Pride
Project description:To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter (RIP). Aire-deficiency reduced the number of mature single positive (SP) OVA-specific CD4+ or CD8+ T cells in the thymus, independent of OVA expression. Importantly, it also contributed in two way to OVA-dependent negative selection depending on the T cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to mTEC-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTEC can mediate tolerance by direct presentation of Aireregulated antigens to both CD4 and CD8 T cells.
2011-04-06 | GSE28393 | GEO
Project description:To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter (RIP). Aire-deficiency reduced the number of mature single positive (SP) OVA-specific CD4+ or CD8+ T cells in the thymus, independent of OVA expression. Importantly, it also contributed in two way to OVA-dependent negative selection depending on the T cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to mTEC-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTEC can mediate tolerance by direct presentation of Aireregulated antigens to both CD4 and CD8 T cells. Total RNA was extracted from medullary thymic epithelial cells isolated from wildtype and Aire-deficient C57BL/6 mice for comparison of gene expression profiles.
2011-04-06 | E-GEOD-28393 | biostudies-arrayexpress
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:Profiling whole lung from Ovalbumin (OVA)-challenged and control BALB/c mice
| PRJNA155287 | ENA
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:To establish cancer cells escaping from host immunity, we used murine B16 melanoma cell line expressing ovalbumin (B16OVA) and inoculated into mice immunized with OVA. Using this model, we established cell lines after the in vivo passage through distinct immunological condition. B16OVA tumor exposed to OVA-specific CD8+ T cell immunity in OVA-immunized B6 mice were isolated and established five variants (IMM1, 2, 8). For comparison, B16OVA tumors from non-immunized naïve B6 mice or OVA-immunized IFN-gamma-deficient mice were also isolated and established four variants, namely NIMM (1, 3, 4) cell lines or GKO-IMM (1, 2, 3) cell lines, respectively.
2022-03-29 | GSE199573 | GEO
Project description:Abatacept is a recombinant CTLA-4 moleculed fused to a mutated human IgG molecule, which is clinically used in rheumatoid arthritis by inhibiting CD28-costimulation. This study aimed to inverstigate the ability of abatacept -mediated costimulation blockade to induce antigen-specific tolerance during primary immune responses. This is important as some studies have suggested that costimulation blockade can lead to CD4+ T cell anergy which could be beneficial for early therapy of autoimmune diseases such as rheumatoid arthritis. In addition we also investigated the effect that abatacept has on CD11c+ antigen presenting cells. This is important as costimulation blocakde can affect the biderectional interaction between CD4+ T cells and CD11c+ cells influencing the immunological outcome. We used microarrays to identify if abatacept treatment leads to antigen specific anergy using transgenic animals and models of priming and oral tolerance that established a synchronised monoclonal response. In addition this magnified the effect on the CD11c+ antigen presenting cells. This study included 5 experimental groups. DO11.10 RAG2-/- mice have CD4+ T cells specific for the ovalbumin (OVA) peptide OVA323-339. These mice were immunised with CFA/OVA s.c. (primed group) or tolerised by feeding with OVA (50mg/kg) in the drinking water. CD4+ cells were isolated 10 days post immunisation from draining lymph nodes (LNs) of unimmunised (pooled LNs and Spleen), orally tolerised (mesenteric LNs), primed (axillary LNs), primed treated with control IgG (axillary LNs) and primed treated with abatacept (axillary LNs). For CD11c+ cells cells were isolated by pooled secondary lymphoid organs (LNs and spleen).
2014-10-07 | E-GEOD-62089 | biostudies-arrayexpress