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Comparison of stable human Treg and Th clones by transcriptional profiling - experiment I

ABSTRACT: The aim of this work was to identify functional features that are specific of human Treg cells, through the identification of genes that are differentially expressed: 1/ in activated Treg clones versus activated Thelper clones; 2/ in Th clones activated in the presence versus the absence of TGFb; 3/ in suppressed Th clones, i.e. Th clones activated in the presence of Treg clones, versus controls. Keywords: TCR activation

ORGANISM(S): Homo sapiens

PROVIDER: GSE14330 | GEO | 2009/01/09

SECONDARY ACCESSION(S): PRJNA111445

REPOSITORIES: GEO

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Transcription profiling of human Treg and Th clones - experiment I

Project description:The aim of this work was to identify functional features that are specific of human Treg cells, through the identification of genes that are differentially expressed: 1/ in activated Treg clones versus activated Thelper clones; 2/ in Th clones activated in the presence versus the absence of TGFb; 3/ in suppressed Th clones, i.e. Th clones activated in the presence of Treg clones, versus controls. Experiment Overall Design: Two to four million cells of human T cell clones were collected at rest (time point = 0) or after activation with coated anti-CD3 and soluble anti-CD28 antibodies (time points = 6, 24 or 41hrs). RNA was extracted for hybridization on Affymetrix microarrays.

2009-01-17 | E-GEOD-14330 | biostudies-arrayexpress

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2008-06-13 | E-GEOD-4527 | biostudies-arrayexpress

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Project description:CD4+Foxp3+ regulatory T cells (Treg) are essential for immune homeostasis and maintenance of self-tolerance. They are produced in the thymus and also generated de novo in the periphery in a TGFB dependent manner. Foxp3+ Treg are also required to achieve tolerance to transplanted tissues when induced by co-receptor or costimulation blockade. Using TCR transgenic mice to avoid issues of autoimmune pathology we show that Foxp3 expression is necessary and sufficient for tissue tolerance by coreceptor blockade. Moreover, the known need in tolerance induction for TGFB signalling to T cells, can wholly be explained by its role in induction of Foxp3, as such signalling proved dispensable for the suppressive process. We analysed the relative contribution of TGFB and Foxp3 on the transcriptome of TGFB induced Treg. TGFB elicited a large set of downregulated signature genes. The number of genes uniquely modulated due to the influence of Foxp3 alone was surprisingly limited. Retroviral conditional Foxp3 expression proved sufficient to confer transplant-suppressive potency on CD4+ T cells, and was lost once nuclear Foxp3 expression was extinguished. Thus despite the large genetic influence of TGFB exposure on iTreg the crucial Foxp3 influenced signature independent of TGFB is small. These data support a dual role for TGFB and Foxp3 in induced tolerance, where TGFB stimulates Foxp3 expression whose sustained expression is associated with acquisition of tolerance 21 samples were analyzed. 5 replicates of Marilyn.Foxp3hCD2 activated (HY)(Untreated) and TGFB-induced (HYT) cells sorted as CD4+hCD2+ and CD4+hCD2- and 3 replicates of Marilyn.Foxp3-/- activated and TGFβ-experienced (but Foxp3-) cells sorted as CD4+CD2. Pairwise comparisons were generated for the Marilyn Foxp3hCD2 UT versus TGFB induced populations and also for the Marilyn Foxp3-/- UT versus the TGFB experienced cells sorted as CD4+CD2

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Gene expression of Th cells, macrophages and monocytes derived from WT and Tbx21-/- Th cell-induced colitis

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Human activated Treg cells and retrovirally engineered Th cells, transduced with GARP, FOXP3 or control GFP vector

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2009-04-20 | E-GEOD-13234 | biostudies-arrayexpress

RNA sequencing of human regulatory T cell clones, both Faecalibacterium prausnitzii-reactive DP8a (CD4,CD8alphalow) Tregs and (CD4,CD25high,CD127low) Foxp3 Tregs obtained from the colon lamina propria and from the blood.

Project description:We generated human DP8a Treg (CD4, CD8alow, CCR6+, CXCR6+, F. praunsitzii-reactive) and FoxP3 Treg (CD4, CD25high, CD127low) clones from healthy colon lamina propria-derived lymphocytes (LPL) (from colorectal cancer patients) and from blood lymphocytes from healthy volunteers). Through DEseq2 analysis) we identified activation-induced genes in these clones and compared gene expression between resting and activated DP8a and Foxp3 clones.

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