Transcription profiling of activated and tolerant CD4+ T cells of Tg4 TCR transgenic mice to discover differentially expressed genes with the aim of gaining new insights about the molecular and genetic basis underlying autoimmune disease
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
DISEASE(S): Represent tolerant CD4+ T cells that have not been activated
SUBMITTER: sabah khalid
PROVIDER: E-MEXP-283 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. This SuperSeries is composed of the following subset Series: GSE21379: Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH) GSE21380: Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh Refer to individual Series
2010-04-28 | E-GEOD-21381 | biostudies-arrayexpress
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) WT and Sh2d1a-/- follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.
2010-04-28 | E-GEOD-21379 | biostudies-arrayexpress
Project description:Single-cell RNA-seq from CD4+ T lymphocytes from uninfected steady-state mouse, two mice with Salmonella typhimurium infection at day 14 and one mouse at day 49 post-infection. Used to demonstrate application of reconstruction and analysis of T cell receptor sequences from single-cell RNA-seq.
2016-03-06 | E-MTAB-3857 | biostudies-arrayexpress
Project description:Gene expression analysis of tumor-specific CD8 T cells encountering a tumor-specific antigen in pre-malignant lesions in the liver at different time points post tumor initiation. The overall goal of this mouse study was to elucidate the molecular program in tumor-specific T cells encountering a tumor-specific antigen in pre-malignant lesions. The study identifies the genes and pathways that are dysregulated in tumor-specific T cells associated with T cell unresponsiveness in tumors. To identify the genes and pathways that are dysregulated in tumor-specific T cells. Gene signatures of the following sample groups were compared: 1. Naïve CD8 T cells; 2. Effector CD8 T cells; 3. Dysfunctional tumor-specific CD8 T cells isolated from pre-malignant lesions 8-12 days after tumor induction. 4. Dysfunctional tumor-specific CD8 T cells isolated from pre-malignant lesions 32-34 days after tumor initiation. The mouse tumor model that was used is an autochthonous, tamoxifen-inducible liver cancer model (ASTxCre-ERT2; AST=Albumin-floxStop-SV40 large T antigen; Cre-ERT2 = TAM-dependent Cre-recombinase) in which the SV40 large T antigen serves as the oncogenic driver and tumor-specific antigen; SV40-I TCR transgenic mice, whose CD8 T cells express a Db-restricted TCR specific for the Tag epitope I were used as source of naïve tumor-specific CD8 T cells (TCRSV40-I) Total RNA was isolated from flow-sorted transgenic CD8 TCRSV40-I T cells from the following sample groups: Naïve, effector, D8-12-pre-malignant lesions, and D32-34 pre-malignant lesions.
2016-08-11 | E-GEOD-60501 | biostudies-arrayexpress
Project description:Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection. A paper including data analysis of these experiments has been accepted for publication (Robert J. Johnston et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of follicular helper CD4 T cell differentiation). Experiment Overall Design: Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high), versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.
2009-08-07 | E-GEOD-16697 | biostudies-arrayexpress
Project description:The present study aims to evaluate the alterations induced by type I diabetes and the associated hyperglycemia on the proteome of renal tissue using a transgenic experimental animal model. Diabetic and non-diabetic kidney samples were analyzed by liquid nano-chromatography mass spectrometry and protein abundance was evaluated bylabel free quantification.
2020-09-24 | PXD018053 | Pride
Project description:Microarray analysis was performed on BWF1 mice spleenocyte cells in control and pCONS treated mice. Microarray analysis identified many genes differentially expressed in control vs pCONS treated mice spleenocytes. Some of the genes were uperegulated and some of the genes were down regulated. Microarray analysis was performed in CD4, CD8, and whole spleenocyte WBC cells. Experiment Overall Design: RNA was isolated from the mice spleenocytes from control and pCONs treated mice one week after treatment.
2008-11-13 | E-GEOD-13364 | biostudies-arrayexpress
Project description:Expanded HA-specific Thy-1.1 Tregs were cultured in the presence of HA-pulsed dendritic cells and rhIL-2 with or without HA-specific Teffs. After 5 days, Tregs were sorted by flow cytometry, based on the expression of the Thy-1.1 congeneic marker. Two biological duplicates were hybridized to the Sentrix BeadChips Array mouse WG-6 v2 (Illumina, USA). Data extraction and normalization was performed using Quantile normalization in the BeadStudio software.
2009-09-08 | E-MTAB-146 | biostudies-arrayexpress
Project description:The present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile. In vitro generated P14 TCR cytotoxic T cells were retrovirally infected with a construct encoding GFP-HDAC7 phosphorylation deficient mutant, sorted in base of GFP expression (GFP positive and GFP negative) and processed for microarray analysis in three biological replicas.
2011-03-13 | E-GEOD-27092 | biostudies-arrayexpress
Project description:CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here. The SMARTA TCR transgenic / adptive transfer system was used to identify and sort subsets of antigen-specific CD4 T cells (based on their expression of Ly6c and CXCR5) elicited after acute infection with LCMV (Arm).
2013-04-22 | E-GEOD-43863 | biostudies-arrayexpress