Out-of-Sequence Signal 3 Paralyzes Primary CD4+ T Cell Dependent Immunity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE71124 | GEO | 2015/07/21
SECONDARY ACCESSION(S): PRJNA290398
REPOSITORIES: GEO
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2017-08-28 | PXD004291 | Pride
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. transcriptome of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-58684 | biostudies-arrayexpress
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. RNA sequencing of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-59846 | biostudies-arrayexpress
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. Targeted bisulfite sequencing of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-59858 | biostudies-arrayexpress
Project description:Expression data from mouse tumor-specific CD4+ T cells The central role of tumor-specific Th1 cells in fighting cancer is becoming increasingly appreciated. However, little is known about how these cells are generated in vivo. Here, we used flow cytometry and gene expression microarrays to characterize the primary activation and Th1 differentiation of naïve tumor-specific CD4+ T cells in a mouse model for cancer immunosurveillance. We took advantage of T cell receptor-transgenic mice where CD4+ T cells recognize a tumor-specific antigen secreted by the major histocompatibility complex (MHC) class II-negative MOPC315 myeloma. Cancer cells were injected subcutaneously and T cell activation was analyzed in draining lymph nodes and at the incipient tumor site at day +8. After activation and migration to the incipient tumor site, tumor-specific CD4+ T cells had 29 up-regulated molecules (CD2, CD5, CD11a, CD18, CD25, CD28, CD44, CD45, CD49d, CD51, CD54, CD69, CD71, CD83, CD86, CD90, CD95, CD102, CD122, CD153, CD166, CD200, CD249, CD254, CD274, CD279, Ly6C, MHC class I, and CCR7) and 5 down-regulated molecules (CD27, CD31, CD45RB, CD62L, and CD126) on the surface. The activated CD4+ T cells produced interferon , a cytokine consistent with Th1 polarization, and also interleukin 2 (IL-2), IL-3, IL-10, and tumor necrosis factor . Activation of naïve tumor-specific CD4+ T cells in draining lymph node resulted in the up-regulation of 609 genes and down-regulation of 284 genes. Bioinformatics analysis of genes differentially expressed identified functional pathways related to tumor-specific Th1 cell activation. This study may represent a useful resource to guide the development of Th1-based immunotherapy for cancer. TCR-transgenic SCID mice (n = 12-15) were injected s.c. on the flank with 10(5) MOPC315 cells suspended in 250 µl ice-cold growth factor-reduced Matrigel. At day +8, draining axillary LN were dissected out and pooled, single-cell suspensions were made and staining with mAb was carried out. Activated tumor-specific CD4+ GB113+ T cells were sorted by FACSAria (≥ 95% pure) in three independent experiments. Naïve tumor-specific CD4+ control T cells were obtained from pooled LN from naive TCR-transgenic SCID mice and treated identically in two independent experiments.
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2014-06-25 | E-GEOD-42812 | biostudies-arrayexpress
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