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Global chromatin accessibility of gene locus in CD4+ T cells activated with or without OX40 costimulation

ABSTRACT: OX40 is a T cell costimulatory molecule in the tumor necrosis factor receptor (TNFR) superfamily. Unlike other costimulatory molecules, OX40 is not expressed by naive T cells, but its expression is rapidly induced following T cell activation, and OX40 costimulation plays a critical role in cell survival, proliferation, and generation of memory cells. We used ATAC-seq to detail the chromatin accessibility of gene locus of activated CD4 T cells with or without OX40 costimulation in the presence of TGF-β1 and IL-2 and identified distinct classes of genes after OX40 costimulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE114568 | GEO | 2018/05/18

REPOSITORIES: GEO

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Expression data from C57/Bl6 Wt mice CD4+ T cells after activation with anti-CD3 plus Wt APC or OX40L-Tg APC

Project description:OX40 is a T cell costimulatory molecule in the tumor necrosis factor receptor (TNFR) superfamily. Unlike other costimulatory molecules, OX40 is not expressed by naive T cells, but its expression is rapidly induced following T cell activation, and OX40 costimulation plays a critical role in cell survival, proliferation, and generation of memory cells. We used microarrays to detail the global programme of gene expression of activated CD4 T cells underlying OX40 costimulation and identified distinct classes of up-regulated genes after OX40 costimulation.

2018-05-15 | GSE104611 | GEO

Gene expression analysis of OX40-triggered mouse Treg

Project description:Regulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor. Total RNA obtained from sorted mouse FoxP3-GFP+ Treg activated in vitro with anti-CD3 in the presence of an OX40-agonist mAb (OX86) or isotype control.

2011-09-25 | E-GEOD-32373 | biostudies-arrayexpress

Global chromatin accessibility of gene locus in CD4+ T cells activated with or without OX40 costimulation

Project description:Global chromatin accessibility of gene locus in CD4+ T cells activated with or without OX40 costimulation

| PRJNA471813 | ENA

FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells

Project description:Background: OX40 (CD134) is a co-stimulatory molecule of the tumor necrosis factor receptor (TNFR) superfamily, that is currently investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic αOX40 antibodies in treatment of cancer patients has fallen short of the high expectation in earlier stage trials. Methods: Using lymphocytes from resected tumor, tumor-free tissue and PBMC of 4 hepatocellular and colorectal cancer patients, we performed RNA-Seq to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs). Results: The transcriptional landscape of CD4+ and CD8+ TILs shifted towards a pro-survival, inflammatory and chemotactic profile upon treatment with αOX40_v12.

2020-06-22 | GSE152904 | GEO

Gene expression analysis of OX40-triggered mouse Treg

2011-09-26 | GSE32373 | GEO

Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells

Project description:The choice of costimulatory domain in CAR design dictates the kinetics of in vivo anti-tumor responses, affecting potency, quality and durability. We show that 1928z results in more vigorous effector functions, whereas 19BBz design compensates for their lesser cytotoxic potency by steadily building up their numbers. Therapeutic function can be further improved by combining CD28 and 4-1BB costimulation. 1928z-41BBL was revealed to provide optimal combined costimulation, exhibiting highly therapeutic efficiency with balanced T cell effector function and accumulation. Endogenous IFN-β/IRF7 pathway activation was found in 1928z-41BBL T cell and is required for effector function acquisition. The role of the IFN-β/IRF7 pathway provides a novel mechanism through which engineering T cells improve therapeutic effect by self-providing ‘signal 3’.

2016-04-19 | GSE68329 | GEO

Gene expression analysis of Ox40-cre/ROSA-YFP CD4+ T cell subsets

Project description:An Ox40-cre allele was used for lineage marking of CD4 T cells. Naive T cells that had previously expressed OX40 demonstrated a partially activated phenotype that was distinct from that of the majority of naive T cells. These results are consistent with a minor subpopulation of naive T cells being dependent on strong signaling responses to thymic self ligands. Keywords: T cell population comparison. Characterization of a novel subpopulation of naive T cells. Four types of T cells were sorted from mice (naive, CD44lo, CD44hi and Treg).

2010-04-03 | E-GEOD-13502 | biostudies-arrayexpress

ICOS costimulation is indispensable for the differentiation of T follicular regulatory cells

Project description:ICOS is a T cell costimulatory receptor critical for Tfh cell generation and function. However, the role of ICOS in Tfr cell differentiation remains unclear. Using Foxp3-Cre-mediated ICOS knockout (ICOS FC) mice, we show that ICOS deficiency in Treg-lineage cells drastically reduces the number of Tfr cells during GC reactions but has a minimal impact on conventional Treg cells. Single-cell transcriptome analysis of Foxp3+ cells at an early stage of the GC reaction suggests that ICOS normally inhibits Klf2 expression to promote follicular features including Bcl6 upregulation. Further, ICOS costimulation promotes nuclear localization of NFAT2, a known driver of CXCR5 expression. Notably, ICOS FC mice had an unaltered overall GC B cell output but showed signs of expanded autoreactive B cells along with elevated autoantibody titers. Thus, our study demonstrates that ICOS costimulation is critical for Tfr cell differentiation and highlights the importance of Tfr cells in maintaining humoral immune tolerance during GC reactions.

2023-02-02 | GSE164995 | GEO

Response of expanded human conventional and regulatory T cells to CD28 or TNFR2 costimulation [Exp2]

Project description:Immune responses depend on a dynamic balance between the opposing activities of conventional (Tconv) and regulatory (Treg) CD4+ T cells. While receptor-targeted approaches have been developed based on their modulation of Tconv cells, Tconv and Treg cells share many costimulatory receptors. We aim to determine key differential signaling events downstream of costimulation to find opportunities for selective manipulation of Tconv or Treg cells. This data set includes the transcriptomes of expanded human Tconv and Treg cells that were treated with anti-CD3, anti-CD3/CD28 or anti-CD3/TNFR2 agonistic mAbs for 24 hours.

2020-07-10 | GSE138604 | GEO

Gene expression analysis of OX40+ Tregs from human liver tissues

Project description:Analysis of the gene signature of OX40+ Tregs, in comparison to OX40- Tregs and Tconvs, freshly isolated from liver cirrhosis and tumor of chronic HCV patients. Results provide insights into the metabolic mechanisms of Treg proliferation in premalignant/malignant contexts.

2018-06-26 | GSE103523 | GEO

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