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Microarray analysis of chimeric CD4+CD28null and CD4+CD28+ T-cells in humanized mice.

ABSTRACT: The major goal of this experiment was to identify the overall changes in gene expression of human CD4+CD28 null T-cells that develop after repetitive [xeno] antigen stimulation, in comparison to normal CD4+CD28+ T-cells. These cells were derived by adoptive transfer of human CD4 T-cells from a normal donor (all CD28+) into immunodeficient mice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE28484 | GEO | 2015/01/05

SECONDARY ACCESSION(S): PRJNA139315

REPOSITORIES: GEO

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Microarray analysis of chimeric CD4+CD28null and CD4+CD28+ T-cells in humanized mice.

Project description:The major goal of this experiment was to identify the overall changes in gene expression of human CD4+CD28 null T-cells that develop after repetitive [xeno] antigen stimulation, in comparison to normal CD4+CD28+ T-cells. These cells were derived by adoptive transfer of human CD4 T-cells from a normal donor (all CD28+) into immunodeficient mice. Chimeric human CD4+CD28+ were isolated from 4 mice, and chimeric human CD4+CD28 null cells from two of these animals after expansion and T-cell differentiation in vivo. Animals were euthanized, and single cell suspensions of splenocytes derived. CD4 T-cell subpopulations were isolated by fluoresence activated cell sorting, RNA was extrated, labeled and hybridized to whole human gene expression arrays. Overall changes in the gene expression were identified using GEDI (gene expression dynamic inspector). 603 genes were found to be statistically significant (P<0.05) between the CD4+CD28+ and CD4+CD28null cells. Candidate genes were validated using qRT-PCR

2015-01-05 | E-GEOD-28484 | biostudies-arrayexpress

Expression data from chimeric antigen receptor transduced (CAR) human CD4+ T cells during expansion

Project description:In this data set we include expression data from human CD4+ T cells isolated on day 0, 6, 11 and 24 follow anti-CD3/anti-CD28 magnetic bead stimulation and chimeric antigen receptor transduction. 30 samples were submitted. Samples represented three biological replicates of normal donors transduced with various CARs. CARs used were a cMet 28z specific CAR comprised of the IgG4 hinge, CD28 transmembrane and CD28 and CD3zeta intracellular domains. A CD19 CD28 CAR was specific to CD19, and was comprised of a CD8a hinge, CD28 transmembrane and CD28 and CD3zeta intracellular domain. A third CAR, the CD19 BBz, was used that was specific to CD19 was comprised of a CD8a hinge, CD8a transmembrane and 4-1BB and CD3zeta intracellular domains. Expression data was analyzied on day 0, 6, 11 and 24.

2015-01-14 | E-GEOD-64914 | biostudies-arrayexpress

Creld1-deficient CD4+ T cells under homeostatic condition and CD3/CD28 stimulation

Project description:Transciptome profiling of sorted naive CD4+ T cells from control or Creld1 conditional KO mice (CD4-Cre) both directly ex vivo and with or without stimulation with anti-CD3/anti-CD28 antibodies to study the impact of Creld1 on T cell biology

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Methylation profiling of healthy human CD4+ cells after CD3 and CD28 stimulation

Project description:Genome-wide DNA methylation reference profiles of CD4+ cells after CD3 and CD28 stimulation in two healthy human individuals using the MeDIP technique a custom oligonucleotide array targetting the vast majority of annotated TSSs and non-promoter CGIs in the human genome.

2010-03-23 | E-MTAB-207 | biostudies-arrayexpress

Analysis of Th17 gene signature in the presence of CD28 costimulation in human CD4 naïve T cells

Project description:We determined differentially regulated gene expression profile in CD4 naïve T cells cultured in presence or absence of Th17 inducing cytokines (IL23+IL1β) and anti-CD28. We reported that CD28 costimulation induced Th17-suppressive gene signature.

2018-03-12 | GSE110097 | GEO

CD28 regulation of global alternative splicing changes in activated human CD4+ T cells

Project description:Alternative splicing consists of exons that are selectively either included or excluded from the mature mRNA transcript. Previous studies have demonstrated that ~10-15% of alternatively spliced genes undergo signal-induced changes in isoform abundance in activated primary human CD4+ T cells. In the past, signal-induced alternative splicing changes in T cells have been characterized in the context of CD3 and CD28 activation. CD3 is a component of the T Cell Receptor (TCR) which is responsible for recognizing foreign peptides presented on antigen presenting cells. CD28 enhances various signaling events downstream of the TCR to boost the survival of T cells and is required for full T cell stimulation. The contribution of CD28 signaling to transcriptional changes has been well documented, but the impact on splicing has not been investigated. Here we test the hypothesis that CD28 exerts some of its functional impact through the enhancement of splicing changes in stimulated T cells. We utilized poly(A) RNA-seq and the MAJIQ alternative splicing algorithm to analyze splicing events of human CD4+ T cells stimulated with through CD3 in the presence and absence of co-stimulation with CD28. Consistent with previous studies, we identified approximately 400 and 1,000 significant splicing events induced by CD3/CD28 stimulation at 8 and 48 hours of culture, respectively. Alternative splicing changes induced by CD3 and CD3/CD28 stimuli are highly correlative, however, approximately 23% of alternative splicing changes are further enhanced with additional CD28 costimulation at 8 hours of culture. This enhancement drops to 8% of alternative splicing events by 48 hours. Therefore, we conclude that CD28 costimulation increases the magnitude of splicing during T cell activation, in a manner that is eventually compensated for over time with CD3 stimulation alone.

2020-06-13 | GSE135118 | GEO

Whole-genome expression profiles of CD4+ CD28+ and CD4+ CD28null T lymphocytes.

Project description:The loss of the CD28 co-stimulatory molecule by CD4+ lymphocytes (CD28null T cells) is accompanied by the acquisition of new biological and functional properties that lead to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset in several inflammatory disorders and in healthy individuals, mainly in aging, are yet a controversial point. Here, we provide the whole-genome DNA methylation and gene expression profiles of CD28null T cells and its CD28+ counterpart. A comparative analysis reveals that 296 genes are differentially methylated between both cell subsets. One hundred sixty (160 genes) associated with the cytotoxicy ability (e.g., GRZB, TYROBP, and RUNX3) and cytokine/chemokine signaling (e.g., CX3CR1, CD27, and IL1R) are demetylated in CD28null T cells, whilst 136 de-novo methylated genes matched with defects in the TCR signaling pathway (e.g., ITK, TXK, CD3G, and LCK). Moreover, we show that genes related inflammasome activation are differentially expressed between CD28null and CD28+ T cells, highlight the contribution of this pathways to the pro-inflammatory profile of CD28null T cells. Overall, our results reveal that CD28null T cells have a unique DNA methylation landscape, which is associated with alteration in gene expression and contributes to the functionality of these cells. Understanding these epigenetic regulatory mechanisms could provide novel therapeutic strategies to prevent the accumulation and activation of these cells in aging and inflammatory disorders.

2016-12-15 | GSE78941 | GEO

Specific transcriptional programs differentiate ICOS and CD28 co-stimulatory signals in human naïve CD4 + T cells

Project description:a global transcriptome profiling was performed by RNA-seq on naïve CD4+ T cells upon ICOS or CD28 co-stimulation and bioinformatically was revealed a set of pathways specifically associated to each costimulatory molecule.

2022-08-11 | GSE191040 | GEO

Expression data from chimeric antigen receptor transduced (CAR) human CD4+ T cells during expansion

2015-01-14 | GSE64914 | GEO