Regulatory T cells restrain IL-2- and Blimp-1-dependent acquisition of cytotoxic function by CD4+ T cells
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PROVIDER: PRJNA593835 | ENA |
REPOSITORIES: ENA
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Project description:In addition to helper and regulatory potential, CD4+T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4+T cells following immunotherapy. CD4 transfer into lymphodepleted animals or regulatory T cell (Treg)depletion promoted GzmB expression by tumor-infiltrating CD4+which was prevented by IL-2 neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized bythe expression of the transcription factors T-bet and Blimp-1. Whilst T-bet ablation restrictedIFN-gproduction, lossof Blimp-1preventedGzmB expressionin response to IL-2, suggesting these are two independent programs required forpolyfunctionality of tumor-reactive CD4+T cells. The data underscores the role of Treg, IL-2 and Blimp-1 controlling the differentiation of cytotoxic T cells and offers a pathway to enhancement of anti-tumor activity through their manipulation.
2019-12-18 | GSE141540 | GEO
Project description:In addition to helper and regulatory potential, CD4+ T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4+ T cells following immunotherapy. CD4+ transfer into lymphodepleted animals or regulatory T (Treg) cell depletion promoted GzmB expression by tumor-infiltrating CD4+, and this was prevented by interleukin-2 (IL-2) neutralization. Transcriptional analysis revealed a polyfunctional helper and cytotoxic phenotype characterized by the expression of the transcription factors T-bet and Blimp-1. While T-bet ablation restricted interferon-? (IFN-?) production, loss of Blimp-1 prevented GzmB expression in response to IL-2, suggesting two independent programs required for polyfunctionality of tumor-reactive CD4+ T cells. Our findings underscore the role of Treg cells, IL-2, and Blimp-1 in controlling the differentiation of cytotoxic CD4+ T cells and offer a pathway to enhancement of anti-tumor activity through their manipulation.
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2013-09-05 | E-GEOD-40587 | biostudies-arrayexpress
Project description:Expression of Blimp-1 was specifically deleted in dendritic cells (DCs) by breeding Blimp-1 flox and CD11c-CRE mice. MiRNA expression was evaluated and compared from DCs, CD4+ T cells and total B cells from spleens of control and Blimp-1 KO mice.
2013-09-05 | GSE40587 | GEO
Project description:The goal of this study was to profile Blimp1 binding in E18.5 small intestine using a Blimp-1-eGFP knock-in allele, and to compare Blimp-1-eGFP genomic binding with Irf-1 genomic binding in normal small intestine. Changes in Irf-1 binding between wild type and Prdm1/Blimp-1 mutant small intestine were also assessed. ChIP-seq was performed for Blimp-1-eGFP in duplicate in E18.5 small intestine expressing the fusion protein using anti-GFP antibody. As a negative control a single anti-GFP ChIP was also performed in wild type small intestine. ChIP-seq for Irf-1 was performed in duplicate in both wild type and Prdm1/Blimp-1 mutant E18.5 small intestine using an anti-Irf-1 antibody. Duplicate IgG ChIP control in wild types was performed as a negative control. All samples had an associated input chromatin sample sequenced.
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2018-12-20 | GSE111416 | GEO
Project description:Antigen-specific effector CD8+ T cells deficient in Blimp-1 (Prdm1) do not acquire maximal effector functions, evade terminal differentiation, and more rapidly acquire some hallmark properties of memory CD8+ T cells. In this study, we compared the gene expression profiles of wildtype and Prdm1-/- LCMV-specific effector CD8+ T cells to better understand the molecular mechanisms underlying this striking phenotype. DNA microarray analysis was performed of DbGP33-41 and DbNP396-404 tetramer-positive effector CD8+ T cells FACS-sorted at day 8 post-LCMV infection from four independent samples of either Blimp-1 conditional knockout mice (CKO; Blimp-1flox/flox x GranzymeB-cre+) or wildtype (WT) littermate controls.
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