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Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs

ABSTRACT: Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs

PROVIDER: PRJNA885122 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21742726_1.fastq.gz	Fastqsanger.gz
	SRR21742726_2.fastq.gz	Fastqsanger.gz
	SRR21742727_1.fastq.gz	Fastqsanger.gz
	SRR21742727_2.fastq.gz	Fastqsanger.gz
	SRR21742728_1.fastq.gz	Fastqsanger.gz

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RNA sequencing analysis of ex vivo expanded CD27+CD70- and CD27-CD70+ human regulatory T cells

Project description:Our study shows that after extended stimulation of human CD4+CD25+CD127- Tregs in vitro, a stable cell subset that downregulates CD27 and upregulates CD70 develops. Expanded CD27+CD70- Tregs display a gene profile which closely relates to the previously described “Treg gene signature”, whereas CD27-CD70+ Tregs express some genes associated with Treg gene signature and some genes overexpressed in conventional T cells.

2020-07-10 | GSE129251 | GEO

Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs

Project description:Most T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown. In this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4+ T cells in vivo, in the absence of intentional antigenic stimulation. Our data show that both T cell subsets convert into type 1 effectors, characterized by cell activation, cytokine production, response to IFN-and CXCR3-dependent migration to inflammatory sites. Our data highlight the role of the transcription factor Eomes in this process. We conclude that CD27 may regulate the development of Th1 immunity in peripheral tissues as well as the subsequent switch of the effector response into long-term memory.

2022-11-30 | GSE214395 | GEO

Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs.

Project description:IntroductionMost T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown.MethodsIn this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4+ T cells in vivo, in the absence of intentional antigenic stimulation.ResultsOur data show that both T cell subsets polarize into type 1 Tconvs or Tregs, characterized by cell activation, cytokine production, response to IFN-γ and CXCR3-dependent migration to inflammatory sites. Transfer experiments suggest that CD27 engagement triggers Treg activation in a cell autonomous fashion.ConclusionWe conclude that CD27 may regulate the development of Th1 immunity in peripheral tissues as well as the subsequent switch of the effector response into long-term memory.

| S-EPMC10041113 | biostudies-literature

CD27 costimulation modulates naïve T cell activation through TRAF2/SHP-1 and induces memory-associated gene regulatory networks.

Project description:Engagement of CD27 during naïve CD8+ T (TN) cell activation is critical for T cell memory generation through poorly understood mechanisms. To examine the effects of CD27 signaling during TN cell activation we designed a synthetic trimeric CD70 ligand. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 resulted in immediate receptor internalization, recruitment of TRAF2/SHP-1, and modulation of Lck and ERK/AKT signaling in cells receiving concurrent CD28 costimulation. Independent of this modulatory effect on CD28 costimulated T cells, CD27 signaling enhanced ATF2, FOXO1, and FOXP1 transcription factor circuits, which induced T cell memory rather than the effector associated gene programs observed with CD28 costimulation alone. CD27-costimulated T cells engineered with a chimeric antigen receptor (CAR) exhibited improved tumor control. CD27 signaling during TN cell activation modulates activation strength and directs memory T cell properties that may benefit therapeutic T cells engineered with CARs or T cell receptors.

2023-10-10 | GSE244834 | GEO

RNA sequencing analysis of ex vivo expanded CD27+CD70- and CD27-CD70+ human regulatory T cells

Project description:RNA sequencing analysis of ex vivo expanded CD27+CD70- and CD27-CD70+ human regulatory T cells

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Assessement of transcriptional consequences of CD27 signaling on Tregs during Th17 polarization

Project description:Assessement of transcriptional consequences of CD27 signaling on Tregs during Th17 polarization

| PRJNA498509 | ENA

Transcription profiling by array of mouse wild type or CD27-/- OT-I T cells are stimulated with artficial antigen presenting cell lines expressing CD70 and/or CD80

Project description:WT or CD27-/- OT-I T cells are stimulated in vitro with artficial antigen presenting cell (aAPC) lines expressing CD70 and/or CD80 for 2, 4, 8 or 14 hours.

2010-09-29 | E-NCMF-38 | biostudies-arrayexpress

Single-cell sequencing of human peripheral blood mononuclear cells

Project description:Understanding of the downstream mechanism of CD70-CD27 signaling in Tregs

2023-03-05 | GSE200315 | GEO

Assessement of transcriptional consequences of CD27 signaling on Tregs during Th17 polarization

Project description:The goal of this study was to identify transcripts that were differentially expressed in untreated vs FcCD70 treated Tregs cultured in Th17 promoting conditions.

2018-12-02 | GSE121795 | GEO

Analysis of CD70 wild type or CD70 knock out CD70-specific nanoCAR T cells

Project description:CD70 is an attractive target for chimeric antigen receptor (CAR) T cell therapy as treatment for both solid and liquid malignancies. However, functionality of CD70-specific CAR T cells is only modest. Here, we optimized a CD70-specific VHH based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models in vitro, using co-cultures of CD70-specific nanoCAR T cells with malignant rhabdoid tumor organoids, and in vivo by using a diffuse large B cell lymphoma (DLBCL) patient-derived xenograft (PDX) model. Whereas the nanoCAR T cells were highly efficient in organoid co-cultures, they showed only modest efficacy in the PDX model. Knocking out CD70 expression in the nanoCAR T cells resulted in dramatically enhanced functionality in the PDX model, suggesting that CD70 interaction in cis with the nanoCAR induces exhaustion. Through single-cell transcriptomics, we obtained evidence that CD70 KO CD70-specific nanoCAR T cells are protected from antigen-induced exhaustion. Our data show that CARs targeted to endogenous T cell antigens, negatively affect CAR T cell functionality by inducing an exhausted state, which can be overcome by knocking out the specific target, in this case CD70.

2024-06-17 | GSE227435 | GEO

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