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.
Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4<sup>+</sup> T Cells.
Specimen part
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
View SamplesTransient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sex, Specimen part
View SamplesHuman medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
No sample metadata fields
View SamplesFour vehicle-treated and four HhAntag-treated pancreatic xenograft tumors were profiled for gene expression changes using Affymetrix U133 Plus 2.0 and Affymetrix Mouse Genome 430 2.0 arrays.
A paracrine requirement for hedgehog signalling in cancer.
No sample metadata fields
View SamplesThe experiment consists of 31 Systemic Lupus Erythematosus patient blood samples and 29 healthy donor blood samples. Overall design: Whole blood was collected in PaxGene tubes from 31 SLE and 29 healthy donors.
Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus.
Sex, Age, Specimen part, Subject
View SamplesThis experiment was designed to look for in vitro IL-3 gene signature in donor blood at two different time points (6 and 24 hours). RNA from lysed whole blood cells was used for the sequencing. Overall design: Lysed whole blood from seven healthy donors was stimulated with recombinant human IL-3 for 6 hours, or 24 hours, prior to RNA extraction for next-generation sequencing on the Illumina HiSeq platform. Unstimulated samples were included as controls.
A potential association between IL-3 and type I and III interferons in systemic lupus erythematosus.
Sex, Age, Specimen part, Disease, Treatment, Subject, Time
View SamplesAbout 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesThe purpose of this experiment was to assess the genes upregulated when pDCs were stimulated with TLR7 agonist imiquimod and TLR9 agonist CpG C. Overall design: pDCs were isolated from six healthy donors by FACS sorting, and were stimulated with CpG and imiquimod for 18 hours, after which RNA was extracted for next generation sequencing on the Illumina HiSeq platform. Unstimulated samples were included as controls.
A cytotoxic anti-IL-3Rα antibody targets key cells and cytokines implicated in systemic lupus erythematosus.
No sample metadata fields
View SamplesTo identify genes regulated by AP3/PI, we carried out microarray experiments using an Arabidopsis whole genome GeneChip array (ATH1 GeneChip, Affymetrix, Santa Clara, CA) in conjunction with an inducible AP3-GR system. For these experiments, we used 35S::AP3-GR transgenic plants in a 35S::PI, ap3-3 null mutant background for various dex or mock treatments. RNA was extracted from inflorescences at 0 and 4 hours after dex or a mock treatment and used as probes for our microarray experiments. Three biological replicates of each were hybridized to Affymetrix ATH1 arrays. We used the Affymetrix Microarray Suite software (MAS) to identify genes whose expression profiles changed only after dex-treatment and are likely targets of AP3/PI.
Two GATA transcription factors are downstream effectors of floral homeotic gene action in Arabidopsis.
No sample metadata fields
View Samples