Expression profiling of Treg cell versus their controls in human and mouse
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE4571 | GEO | 2006/05/31
SECONDARY ACCESSION(S): PRJNA94405
REPOSITORIES: GEO
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Project description:We applied Affymetrix GeneChip technology for expression profiling of CD4+CD25+ (Treg) T cells versus their naive CD4+CD25- controls to obtain more information about the underlying molecular mechanisms involved in Treg specific immune suppression Experiment Overall Design: Expression profiles from: Experiment Overall Design: [1] human Treg cells obtained from peripheral blood by cell sorting were compared to their naive controls. RNAs were prepared from pools of ten individual healthy donors, labeled in two independend labeling reactions and hybridized onto two GeneChips of the same lot. Experiment Overall Design: [2] mouse Treg cells obtained from spleen by cell sorting of Balb/c mice were compared to their naive controls. RNAs were prepared from pools of three individual Balb/c mice, labeled in three independend labeling reactions and hybridized onto three GeneChips of the same lot. Experiment Overall Design: The differences in gene expression were used to unravel molecular mechanisms that help to explain the suppressive and anergic phenotypes of Treg cells after antigen activation.
2008-06-13 | E-GEOD-4571 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells play an important role in the induction and maintenance of peripheral tolerance. Treg cells also suppress a variety of other immune responses, including anti-tumor and alloimmune responses. We have previously reported that tumor-activated Treg cells express granzyme B and that granzyme B is important for Treg cell-mediated suppression of anti-tumor immune responses (GSE13409). Here, we report that allogeneic mismatch also induces the expression of granzyme B. Granzyme B-deficient mice challenged with fully mismatched allogeneic P815 mastocytoma cells have markedly improved survival compared to WT and other granzyme- or perforin-deficient mice, suggesting an immunoregulatory role for granzyme B in this setting. Treg cells harvested from the tumor environment of P815-challenged mice express granzyme B. Treg cells also express granzyme B in vitro during mixed lymphocyte reactions and in vivo in a mouse model of graft-versus-host disease (GVHD). However, in contrast to findings from our previously published tumor model, granzyme B is not required for the suppression of effector T cell (Teff) proliferation in in vitro Treg suppression assays stimulated by either Concanavalin A or allogeneic antigen presenting cells. Additionally, in an ex vivo assay, sort-purified in vivo-activated CD4+Foxp3+ Treg cells from mice with active GVHD -- under conditions known to induce granzyme B expression in Treg cells -- suppressed Teff cell proliferation in a granzyme B-independent manner. Adoptive transfer of naive granzyme B-deficient CD4+CD25+ Treg cells into a mouse model of GVHD rescued hosts from lethatlity equivalently to naive wild-type Treg cells. Serum analysis of GVHD-associated cytokine production in these recipients also demonstrated that Treg cells suppressed production of IL-2, IL-4, IL-5, GM-CSF, and IFN-gamma in a granzyme B-independent manner. In order to determine whether the context in which Treg cells are activated alters the intrinsic properties of Treg cells, we used Foxp3 reporter mice to obtain gene expression profiles of CD4+Foxp3+ Treg cells purifed from naive resting spleens, spleens from mice with acute GVHD, and from ascites fluid of mice challenged intraperitoneally with allogeneic P815 tumor cells. Unsupervised analyses revealed distinct activation signatures of Treg cells among the 3 experimental groups. Taken together, these findings demonstrate that granzyme B is not required for Treg cell-mediated suppression of GVHD, which is in contrast to what we have previously reported for Treg cell function in the setting of tumor challenge. Cell intrinsic differences could partially account for these differential phenotypes. These data also suggest the therapeutic potential of targeting specific Treg cell suppressive functions in order to segregate GVHD and graft-versus-tumor effector functions. Experiment Overall Design: Six replicates of Naive CD4+Foxp3+ Treg cells were purified from resting spleens, five replicates of allogeneic tumor-activated Treg cells and three samples of GVHD-activated Treg cells. Experiment Overall Design: Naive reps 1-3 are controls for the GVHD-activated samples. Experiment Overall Design: Naive reps 4-6 are controls for the Allogeneic tumor-activated samples.
2009-09-15 | E-GEOD-16210 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells play an important role in the induction and maintenance of peripheral tolerance. Treg cells also suppress a variety of other immune responses, including anti-tumor and alloimmune responses. We have previously reported that tumor-activated Treg cells express granzyme B and that granzyme B is important for Treg cell-mediated suppression of anti-tumor immune responses (GSE13409). Here, we report that allogeneic mismatch also induces the expression of granzyme B. Granzyme B-deficient mice challenged with fully mismatched allogeneic P815 mastocytoma cells have markedly improved survival compared to WT and other granzyme- or perforin-deficient mice, suggesting an immunoregulatory role for granzyme B in this setting. Treg cells harvested from the tumor environment of P815-challenged mice express granzyme B. Treg cells also express granzyme B in vitro during mixed lymphocyte reactions and in vivo in a mouse model of graft-versus-host disease (GVHD). However, in contrast to findings from our previously published tumor model, granzyme B is not required for the suppression of effector T cell (Teff) proliferation in in vitro Treg suppression assays stimulated by either Concanavalin A or allogeneic antigen presenting cells. Additionally, in an ex vivo assay, sort-purified in vivo-activated CD4+Foxp3+ Treg cells from mice with active GVHD -- under conditions known to induce granzyme B expression in Treg cells -- suppressed Teff cell proliferation in a granzyme B-independent manner. Adoptive transfer of naive granzyme B-deficient CD4+CD25+ Treg cells into a mouse model of GVHD rescued hosts from lethatlity equivalently to naive wild-type Treg cells. Serum analysis of GVHD-associated cytokine production in these recipients also demonstrated that Treg cells suppressed production of IL-2, IL-4, IL-5, GM-CSF, and IFN-gamma in a granzyme B-independent manner. In order to determine whether the context in which Treg cells are activated alters the intrinsic properties of Treg cells, we used Foxp3 reporter mice to obtain gene expression profiles of CD4+Foxp3+ Treg cells purifed from naive resting spleens, spleens from mice with acute GVHD, and from ascites fluid of mice challenged intraperitoneally with allogeneic P815 tumor cells. Unsupervised analyses revealed distinct activation signatures of Treg cells among the 3 experimental groups. Taken together, these findings demonstrate that granzyme B is not required for Treg cell-mediated suppression of GVHD, which is in contrast to what we have previously reported for Treg cell function in the setting of tumor challenge. Cell intrinsic differences could partially account for these differential phenotypes. These data also suggest the therapeutic potential of targeting specific Treg cell suppressive functions in order to segregate GVHD and graft-versus-tumor effector functions. Keywords: Normal vs Activated
2009-08-31 | GSE16210 | GEO
Project description:We used single cell RNA sequencing (scRNA-seq) to analyze the difference among CD25+CD127-Treg, iTreg, and iCD4+Treg-like. We expanded CD25+CD127-Treg by TCR stimulation in the presense of AS2863619, anti-TNFR2 antibody, and TGFbeta (AMT). We differentiated iTreg from naive CD4+T cells and iCD4+Treg-like from iPSC-derived CD4+T cells in the presence of TCR stimulation, AS2863619, anti-TNFR2 antibody, TGFbeta, and rapamycin (AMRT).
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Project description:HDAC10–/– (B6N(Cg)-Hdac10tm1.1(KOMP)Mbp/J) and wild type (WT) CD4+CD25+ Treg were isolated and RNA procured. Single strand cDNA was generated, fragmented and labeled, and hybridized to Affymetrix GeneChip Mouse Gene 2.0 ST Arrays for microarray analysis.
2019-05-28 | GSE131794 | GEO
Project description:This study evaluated changes in gene expression upon IL-7 treatment in human naive and memory Treg. CD4+CD25+CD127low naïve and memory Treg were isolated from fresh PBMC and separately stimulated with ?CD3?/CD28 coupled beads (Invitrogen-Dynal) at a 1:10 bead/T cell ratio, treated with or without 10 ng/ml of rhIL-7 (R&D Systems) for 16 hours. qPCR gene expression profiling of CD4+CD25+CD127low naïve and memory Treg obtained from 2 separate donors. Cell lysates were prepared separately from the 2 donors and pooled prior to RNA extraction.
2012-09-12 | E-GEOD-40755 | biostudies-arrayexpress
Project description:Although several markers have been associated with the characterization of regulatory T cells (Treg) and their function, no studies have investigated the dynamics of their phenotype during infection. Since the necessity of Treg to control immunopathology has been demonstrated, we used the chronic helminth infection model S. mansoni to address the impact on the Treg gene repertoire. Before gene expression profiling we first chose to study the localization and antigen-specific suppressive nature of classically defined Treg during infection. Presence of Foxp3+ cells were found especially in the periphery of granulomas and isolated CD4+CD25hiFoxp3+ Treg from infected mice blocked IFN-gamma and IL-10 cytokine secretion from infected CD4+CD25- effector T cells (Teff). Furthermore the gene expression patterns of Treg and Teff showed that in total 474 genes were significantly regulated during chronic schistosomiasis. Upon k-means clustering we identified genes exclusively regulated in all four populations including Foxp3, CD103, GITR, OX40 and CTLA-4: classical Treg markers. During infection however, several non-classical genes were up-regulated solely within the Treg population such as Slpi, Gzmb, Mt1, Fabp5, Nfil3, Socs2, Gpr177 and Klrg1. Using RT-PCR we confirmed aspects of the microarray data and in addition showed that the expression profile of Treg from S. mansoni-infected mice is simultaneously unique and comparative with Treg derived from other infections Regulatory T cells (Treg) or effector T cells (Teff) were FACS-sorted as CD4+CD25+ or CD4+CD25- from mesenteric lymph nodes (MLN) of naive mice or from mice infected with Schistosoma mansoni. Affymetrix MOE430A 2.0 genechips were used to identify genes differentially expressed in Treg or Teff under resting or infected conditions.
2010-04-12 | E-GEOD-17580 | biostudies-arrayexpress
Project description:CD4+CD25-CD62L+ naive T-cells were FACS isolated from wild type mouse lymph node. These were compared to regulatory T cells (Treg; CD4+C25+) and activated T-cells induced to express Foxp3 by treatment with rapamycin and LY294002 (Treg-like cells). RNA was extracted from duplicate cultures using RNA-Bee, labelled with the Affymetrix GeneChip Small Sample protocol and hybridised to Affymetrix Mouse 430 2.0 Arrays.
2008-07-23 | E-MIMR-1241 | 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:The PI3K pathway has emerged as a key regulator of regulatory T cell (Treg) development and homeostasis and is required for full Treg-mediated suppression. To identify new genes involved in PI3K-dependent suppression we compared the transcriptome of WT and p110delta D910A Tregs. Among the genes that were differentially expressed was CD38. Here we show that CD38 is expressed mainly by a subset of Foxp3+CD25+CD4+ T cells originating in the thymus and on Tregs in the spleen. CD38high WT Tregs showed superior suppressive activity and CD38low Tregs failed to upregulate CD73, a surface protein which is important for suppression. However, Tregs from heterozygous CD38+/- mice were unimpaired despite their lower levels of CD38 expression. Therefore, CD38 can be used as a marker for Tregs with high suppressive activity and the impaired Treg function in p110delta D910A mice can in part be explained by the failure of CD38high cells to develop.
2011-04-01 | E-MEXP-2955 | biostudies-arrayexpress