Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA287705 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Differentiation of naive CD8 T cells into cytotoxic effector cells requires three distinct signals- antigen (signal 1), costimulation -B7-1 (signal 2) and cytokine, either interleukin-12 or interferon-a/b (signal 3). Interaction of naive CD8 T cells with antigen and B7-1 programs cell division and proliferation whereas the presence of cytokines- IL-12 or IFNa/b promote survival, differentiation and memory establishment. In the absence of signal 3, the cells interacting with antigen/B7-1 undergo tolerance induction. The objective of this study was to elucidate the mechanisms how the provision of signal 3 promotes differentiation and averts tolerance induction in CD8 T cells. Trichostatin A is a pharmacological agent that inhibits histone deacetylase activity, hence regulating chromatin structure and gene expression and differentiation in many cell types. Gene signature profiles of IL-12, IFNa/b and trichostatin A stimulated cells were compared to elucidate the molecular mechanisms of gene regulation. Oligonucleotide microarray analysis is carried out to determine the extent and molecular nature of the CD8 T cell differentiation program induced by IL-12 or IFNa/b in concert with antigen and B7-1 signal. Experiment Overall Design: The programming for development of function and memory in presence of signal 3 occurs over three days of initial stimulation, and antigen-B7 and IL-12 or IFNa/b must be present for most of this period to achieve maximal responses. We analyzed gene expression in highly purified naive CD8 T cells at 0, 24, 48 and 72h of in vitro culture stimulated with antigen-B7 and with or without IL-12 or IFNa/b to tease apart gene expression profiles of naive, 2-signal and 3-signal stimulated cells over the course of 3-days. Gene expression of cells stimulated with trichostatin A for 72hr were compared with IL-12 or IFNa/b stimulated cells. 20 arrays.
2009-08-01 | E-GEOD-15930 | biostudies-arrayexpress
Project description:Differentiation of naive CD8 T cells into cytotoxic effector cells requires three distinct signals- antigen (signal 1), costimulation -B7-1 (signal 2) and cytokine, either interleukin-12, interferon-a/b, or IL-21 (signal 3). Interaction of naive CD8 T cells with antigen and B7-1 programs cell division and proliferation whereas the presence of cytokines- IL-12, IFNa/b or IL-21 promote survival, differentiation and memory establishment. In the absence of signal 3, the cells interacting with antigen/B7-1 undergo tolerance induction. Previous work had analyzed the regulation of mRNA expression changes induced by IL-12 and IFN-a and cells stimulated with antigen, B7-1 and cytokine by comparing mRNA expression levels in naïve CD8 T cells, cells stimulated with 2 signals (antigen and B7-1) (Agarwal, P.A., A. Raghavan, S.L. Nandiwada, J.M. Curtsinger, P.R. Bohjanen, D.L. Mueller and M.F. Mescher. Gene regulation and chromatin remodeling by IL-12 and Type I interferon in programming for CD8 T cell effector function and memory. J. Immunol. 183:1695-1704 (2009). PMCID: PMC2893405). That microarray data was deposited in the NCI GEO database and can be found at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc_GSE15930. The objective of the current study was to carry out the same analysis to determine IL-21-dependent changes in mRNA expression in CD8 T cells responding to antigen and B7-1-dependent costimulation in the absence or presence of IL-21.
2015-09-30 | GSE70136 | GEO
Project description:Differentiation of naive CD8 T cells into cytotoxic effector cells requires three distinct signals- antigen (signal 1), costimulation -B7-1 (signal 2) and cytokine, either interleukin-12 or interferon-a/b (signal 3). Interaction of naive CD8 T cells with antigen and B7-1 programs cell division and proliferation whereas the presence of cytokines- IL-12 or IFNa/b promote survival, differentiation and memory establishment. In the absence of signal 3, the cells interacting with antigen/B7-1 undergo tolerance induction. The objective of this study was to elucidate the mechanisms how the provision of signal 3 promotes differentiation and averts tolerance induction in CD8 T cells. Trichostatin A is a pharmacological agent that inhibits histone deacetylase activity, hence regulating chromatin structure and gene expression and differentiation in many cell types. Gene signature profiles of IL-12, IFNa/b and trichostatin A stimulated cells were compared to elucidate the molecular mechanisms of gene regulation. Oligonucleotide microarray analysis is carried out to determine the extent and molecular nature of the CD8 T cell differentiation program induced by IL-12 or IFNa/b in concert with antigen and B7-1 signal.
2009-07-22 | GSE15930 | GEO
Project description:IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven differentiation of naïve CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of eomesodermin and maturation of naïve CD8+ T cells into granzyme B and CD44 expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8+ T cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2, surprisingly, impaired the subsequent anti-tumor function of transferred cells. Gene expression studies revealed a distinct IL-21-program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced anti-tumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8+ T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies. Two-condition experiment: Cytokine-exposed t-cells subsequentially restimulated without cytokine vs. control t-cells without cytokine subsquentially restimulated without cytokine. 3 independent experiments - 1 with experimental RNA labeled with Cy5, control with Cy3, and 2 with dyes-swapped Keywords: Cytokine exposure comparison Comparitive analysis of cytokine effects on lymphocyte gene expression. GSM265712.gpr (S89_1_IL2_0.gpr): Cy3 - control, Cy5 - experimental GSM265713.gpr (S90_1_IL15_0.gpr): Cy3 - control, Cy5 - experimental GSM265714.gpr (S91_1_IL21_0.gpr): Cy3 - control, Cy5 - experimental GSM265715.gpr (S27_2_0_IL2.gpr): Cy3 - experimental, Cy5 - control GSM265716.gpr (S29_2_0_IL15.gpr): Cy3 - experimental, Cy5 - control GSM265717.gpr (S30_2_0_IL21.gpr): Cy3 - experimental, Cy5 - control GSM265718.gpr (S31_3_0_IL2.gpr): Cy3 - experimental, Cy5 - control GSM265719.gpr (S33_3_0_IL15.gpr): Cy3 - experimental, Cy5 - control
2010-05-26 | E-GEOD-10403 | biostudies-arrayexpress
Project description:IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven differentiation of naïve CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of eomesodermin and maturation of naïve CD8+ T cells into granzyme B and CD44 expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8+ T cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2, surprisingly, impaired the subsequent anti-tumor function of transferred cells. Gene expression studies revealed a distinct IL-21-program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced anti-tumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8+ T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies. Two-condition experiment: Cytokine-exposed t-cells subsequentially restimulated without cytokine vs. control t-cells without cytokine subsquentially restimulated without cytokine. 3 independent experiments - 1 with experimental RNA labeled with Cy5, control with Cy3, and 2 with dyes-swapped Keywords: Cytokine exposure comparison
2008-02-13 | GSE10403 | GEO
Project description:Effects of IL-4 on CD8 T cells functions are largely unknown. IL-4 induces survival and proliferation of CD8 T cells, but several studies suggest that IL-4 could also affect several functions of CD8 T cells such as cytotoxicity. Our team has shown that IL-4 repress the expression of Ccl5 in vitro. To define more precisely the impact of IL-4 on CD8 T cells, we performed a whole genome expression microarray analysis of naive and memory CD8 T cells cultured in presence or absence of IL-4. This approach allowed us to define the IL4-gene-expression signature on CD8 T cells. 18 samples were processed. Two populations of F5 naive CD8 T cells were FACS-sorted: samples from each population were incubated 20 hours with IL-7 in presence or absence of IL-4. Thus, a total of 6 “Naive” samples were processed. In addition, 4 populations of F5 TIM memory CD8 T cells were FACS-sorted: samples from 2 of these populations were incubated 20 hours in presence of IL-7 and/or IL-4, or in medium alone. Thus, 12 “Memory” samples were processed.
2011-09-27 | E-GEOD-32423 | biostudies-arrayexpress
Project description:IFN alpha mediated gene expression pattern. The effect of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs. This analysis examined the effects of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs. Magnetically sorted untouched CD8+CD45R0- T cells from three different donors were unstimulated or stimulated with IFNa2b or with anti-CD3/CD28 Beads alone or along with IFNa2b or IFNa5 for 48 hours. Individual mRNA samples were analyzed using HG-U133A 2.0 array gene chips. Keywords: Gene expression analysis after different stimulation Magnetically sorted untouched CD8+CD45R0-T cells from three different donors (named A, B and C) unstimulated or stimulated with IFN alpha 2b or with anti-CD3/CD28 beads alone or along with IFN alpha 2b or IFN alpha 5 for 48 hours.
2010-07-23 | E-GEOD-17301 | biostudies-arrayexpress
Project description:In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. Experiment Overall Design: Sez-4 cell line was starved of IL2 for 16h, washed twice and placed into 6-well plates in 10ml RPMI (10% FBS) for 2 h followed by addition of IL-2 (200U), IL-15 (20ng/mL), or IL-21 (100 ng/ml) or medium alone for 4 h.
2008-04-09 | E-GEOD-8685 | biostudies-arrayexpress
Project description:B7x (B7-H4 or B7S1) is the seventh member of the B7 family and the in vivo function remains largely unknown. Despite new genetic data linking the B7x gene with autoimmune diseases, how exactly it contributes to peripheral tolerance and autoimmunity is unclear. Here we showed that B7x protein was not detected on antigen-presenting cells or T cells in both human and mice, which is unique in the B7 family. As B7x protein is expressed in some peripheral cells such as pancreatic b cells, we utilized a CD8 T cell-mediated diabetes model (AI4ab) in which CD8 T cells recognize an endogenous self-antigen, and found that mice lacking B7x developed more severe diabetes than control AI4ab mice. Conversely, mice overexpressing B7x in the b cells (Rip-B7xAI4ab) were diabetes free. Furthermore, adoptive transfer of effector AI4ab CD8 T cells induced diabetes in control mice, but not in Rip-B7xAI4ab mice. Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of migrating to the pancreas but failed to robustly destroy tissue when encountering local B7x in Rip-B7xAI4ab mice. Although AI4ab CD8 T cells in Rip-B7xAI4ab mice and AI4ab mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in AI4ab mice than in RIP-B7xAI4ab mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells and that local overexpression of B7x on pancreatic b cells is sufficient to abolish CD8 T cell-induced diabetes. AI4 mice developed T1D and Rip-B7x AI4 mice were resistant to T1D. Total RNA was collected and gene expression compared between AI4 CD8 T cells from AI4 and Rip-B7xAI4 mice.
2012-08-21 | E-GEOD-40225 | biostudies-arrayexpress
Project description:Blood CD8 T cells from six healthy blood donors were treated with the TLR7 agonist imiquimod + IL-2 in T cell enriched medium overnight in vitro (the controls were incubated with T cell enriched medium + IL-2 only). After approx. 21 h the in solution digest protocol was started.
2024-04-29 | PXD038621 | Pride