Mus musculus
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ABSTRACT:
PROVIDER: PRJNA147911 | ENA |
REPOSITORIES: ENA
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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: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.
2011-09-28 | GSE32423 | 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. 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:To investigate the impact of paracrine IL-2 signals on memory precursor (MP) cell differentiation., we activated CD8 T cell in vitro in the presence or absence of exogenous IL-2 (ex-IL-2). We assessed the memory differentiation of activated T cells by transfer into virus-infected mice. Both conditions generated CD8 T cells that participate in the ongoing immune response and gave rise to similar memory cells. Conversely, when transferred into a naive host, T cells activated with ex-IL-2 generated a higher frequency of memory cells displaying increased functional memory traits. Single-cell RNA-seq analysis indicated that without ex-IL-2, cells rapidly acquire a MP signature, while in its presence they adopted an effector signature. This was confirmed at the protein level and in a killing assay. Overall, ex-IL-2 delays the transition into MP cells, allowing the acquisition of effector functions that become imprinted in their progeny. These findings may help to optimize the generation of therapeutic T cells.
2024-02-22 | GSE237866 | GEO
Project description:Some unicellular organisms exhibit collective decision-making through intercellular communication once a quorum of members sense an environmental stress. Whether T cells at different states of differentiation may also synchronize their behavior on a population basis through direct interactions remains unclear. We report that memory CD8+ T cells (TMem) directly interact with naive T cells (TN) during priming, affecting the phenotypic, functional, transcriptional and metabolic differentiation of TN-derived progeny. This previously unrecognized, contact and concentration-dependent interaction between naive (TN) and memory CD8+ T cells (TMem) directly enhanced TN effector differentiation through non-apoptotic Fas signaling resulting in downstream Akt pathway activation. TN primed with TMem exhibited significantly impaired persistence and antitumor activity compared with TN primed alone. Disruption of FasL-Fas signaling in TN cells limited differentiation and enhanced anti-tumor immunity while provision of exogenous FasL in the absence of TMem impaired anti-tumor immunity by augmenting TN differentiation. These findings reveal that the full therapeutic potential of TN-derived cells for adoptive immunotherapy requires physical separation from TMem prior to priming or antagonism of Fas-signaling. FACS-sorted in vitro differentiated TMem samples were without stimulation (0 hours) (n=3), and FACS-sorted in vitro differentiated TMem samples were stimulated using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. FACS-sorted naive Pmel-1 CD8+ T cell samples were without stimulation (0 hours) (n=3), and FACS-sorted TN-derived Pmel-1 CD8+ T cell samples were stimulated using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. FACS-sorted TN-derived Pmel-1 CD8+ T cell samples were stimulated in the presence of TMem using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. FACS-sorted in vitro differentiated TMem samples were stimulated in the presence of TN using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. All samples were done in triplicate as biological repeats.
2015-03-01 | E-GEOD-56344 | biostudies-arrayexpress
Project description:Disturbed expression of microRNAs (miRNAs) in regulatory T-cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. Moreover, the technical limitations prevented the analysis of such minute T-cell population as naive and memory Tregs. In this study we have used a microarray approach to comprehensively analyze miRNA expression signatures of naive Tregs (CD4+CD45RO-CD25++), memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO-CD25-) and memory (CD4+CD45RO+CD25-) T-cells (Tconvs) derived from peripheral blood of RA patients, and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based qRT-PCR. We found a positive correlation between increased expression of miR-451 in T-cells of RA patients and disease activity score (DAS28), ESR levels, and serum levels of IL-6. Moreover, we found characteristic, disease and treatment independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (e.g. miR-92a), a general memory phenotype (e.g. miR-21, miR-155), and most importantly miRNAs specifically expressed in both naive and memory Tregs, defining as such the Treg phenotype (i.e. miR-146a, miR-3162, miR-1202, miR-1246a, and miR-4281). MicroRNA profiling was performed in four CD4+ T-cell subsets: naive Tconventional (CD3+CD8-CD45RO-CD25-), naive Tregulatory (CD3+CD8-CD45RO-CD25+), memory Tconventional (CD3+CD8-CD45RO+CD25-), and memory Tregulatory (CD3+CD8-CD45RO+CD25+) derived from 2 healthy controls, and 6 rheumatoid arthritis patients (total n=8).
2014-01-22 | E-GEOD-50646 | biostudies-arrayexpress
Project description:Differentiating i-Mixl1 mESCs cultured in the presence or absence of Doxycycline
| PRJNA174968 | ENA
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