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Gene expression profile of activated CD4 T cells from adults and newborns

ABSTRACT: Given their precipitous encounter with the environment, newborn infants might be expected to possess abundant immunoprotective mechanisms. Paradoxically, their T cells display grossly impaired Th1 anti-bacterial and anti-viral responses. This study identifies factors produced by neonatal CD4 T cells when compared with adult naive CD4 T cells and highlights CXCL8 as a pivotal effector molecule in neonatal T cells. Using Affimetrix microarray we compared gene expression in cord blood derived CD4 T cells with naive CD4 T cells from adults after polyclonal stimulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52129 | GEO | 2014/09/21

SECONDARY ACCESSION(S): PRJNA226909

REPOSITORIES: GEO

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Gene expression profile of activated CD4 T cells from adults and newborns

Project description:Given their precipitous encounter with the environment, newborn infants might be expected to possess abundant immunoprotective mechanisms. Paradoxically, their T cells display grossly impaired Th1 anti-bacterial and anti-viral responses. This study identifies factors produced by neonatal CD4 T cells when compared with adult naive CD4 T cells and highlights CXCL8 as a pivotal effector molecule in neonatal T cells. Using Affimetrix microarray we compared gene expression in cord blood derived CD4 T cells with naive CD4 T cells from adults after polyclonal stimulation. The Affymetrix GeneChip Human Genome 1.0 ST array were used to define gene expression profiles in each of the CD4 T cell samples.

2014-09-21 | E-GEOD-52129 | biostudies-arrayexpress

Innate to adaptive: Human IFN-gamma producing CD4+ T cells can derive directly from CXCL8-producing recent thymic emigrants.

Project description:An unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this 'innate-like' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells’ peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that ‘innate like’ CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells

2017-08-09 | GSE84686 | GEO

RNA sequencing of human primary neonatal Naive CD4+ T cells and adult Naive CD4+ T cells treated with Scr or LINE1 ASOs

Project description:RNA sequencing of human neonatal Naive CD4+ T cells and adult Naive CD4+ T cells treated with Scr or LINE1 ASO to assess functional relevance of LINE1 absence in newborns.

2024-08-30 | E-MTAB-13718 | biostudies-arrayexpress

The histone modification landscape of neonatal CD4+ T cells contributes to decreased T cell receptor signaling

Project description:Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) was performed to establish the H3K4me3 landscape in neonatal and adult naive CD4+ T cells. As development progressed from neonate to adult, naive CD4+ T cells gained the activating mark H3K4me3 at immunologically important promoter sites. Adult naive CD4+ T cells had enrichment of H3K4me3 at genes important in T cell receptor signaling, which was associated with improved markers of activation and cytokine expression in adult naive CD4+ T cells after engagement of the T cell receptor.

2019-12-01 | GSE138378 | GEO

naive T cell heterogeneity after neonatal thymectomy

Project description:The generation of new naive T-cells is dependent on thymic output, but in adults the naive T-cell pool is primarily maintained by peripheral proliferation. Naive T-cells have long been regarded as relatively quiescent cells but recently it was shown that IL-8 production is a signatory effector function of naïve T-cells, at least in newborns. With human aging naïve CD4 T-cell numbers decline but it is not clear whether this is accompanied by (functional) differentiation of naïve T-cells and loss of true naivety. Using a unique cohort of children and adolescents who underwent neonatal thymectomy, we demonstrate that the naive CD4 T-cell compartment in healthy humans is functionally heterogeneous and that this functional diversity is lost after neonatal thymectomy. Thymic regeneration later in life resulted in functional restoration of the naïve T-cell compartment. These data shed further light on functional differentiation within the naive T-cell compartment and the importance of the thymus in naive T-cell homeostasis.

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Neonatal T helper 17 responses are skewed towards an immunoregulatory interleukin-22 phenotype

Project description:We report broad developmental differences in gene expression profiles between neonatal (term) and adult naive CD4 T cells, resulting in non-stereotypic Th17 differentiation responses to TGF-beta.

2020-12-31 | GSE135467 | GEO

Neonatal CD4+ T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response

Project description:The adaptive immune response is coordinated by CD4+ T cells, which determine the type and strength of the immune response and the effector cells involved. It has been reported that CD4+ T cells are less responsive in neonates, leading to low activation of the cellular response and poor antibody production by B cells. This low response is essential for the tolerant window that favors birth transition from the sterile environment in the womb to the outside world but leaves neonates vulnerable to infection, which is still an important health issue. Neonates have a high morbidity and mortality rate due to infections, and the molecular reasons are still understudied. We asked whether the neonatal naive CD4+ T cells have a genomic program that predisposes them to a low response. Therefore, we evaluated the transcriptome and epigenome of human neonatal and adult naive CD4+ T cells. Our results point to a gene expression profile forming a distinct regulatory network in neonatal cells, which favors proliferation and a low T-cell response. Such expression profile is supported by a characteristic epigenetic landscape of neonatal CD4+ T cells, which correlates with the characteristic transcriptome of the neonatal cells. These results were confirmed by experiments showing a low response to activation signals, higher proliferation, and lower expression of cytokines of neonatal CD4+ T cells as compared to adult cells. Understanding this network could lead to novel vaccine formulations and better deal with life-threatening diseases during this highly vulnerable period of our lives.

2024-01-30 | GSE218158 | GEO

Puniya2021 - Naive CD4+ T cell metabolic model

Project description:CD4+ T cells are critical components in the human immune system. They produce cytokines to fight against pathogens and abnormal cells and stimulate other cells, such as B cells, macrophages, and neutrophils, to generate an immune response. Naive CD4+ T cells are precursor cells that can differentiate into T helper - 1, - 2, - 17 (Th1, Th2, Th17) and regulatory T cells (Tregs) subtypes based on the type of pathogens or disease. The naive CD4+ T cell model consists of 5179 reactions, 3153 metabolites, and 1055 genes. Together with Th1, Th2, and Th17 models, the naive CD4+ T cell model helped identify drug targets and repurposable drugs against autoimmune diseases.

2023-11-27 | MODEL1909260003 | BioModels

RNA sequencing of human primary neonatal Naive CD4+ T cells and adult Naive CD4+ T cells treated with Scr or LINE1 ASOs

Project description:RNA sequencing of human primary neonatal Naive CD4+ T cells and adult Naive CD4+ T cells treated with Scr or LINE1 ASOs

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Transcriptional profile of human neonatal cord blood and adult peripheral blood dendritic cells

Project description:A phenotypically and functinoally distinct subset of human blood dendritic cells expressing CD11b is specific of the neonatal environment. We have employed whole genome microarray expression profiling to identify the specific gene signature of CD11b+ cord blood dendritic cells as compared to their adult peripheral blood counterparts. Peripheral blood adult cDC2 (CD20- CD11c+ CD14- BDCA1+ CD11b- ), neonatal cord blood cDC2 (CD20- CD11c+ CD14- BDCA1+ CD11b-) and neonatal cord blood cDC2b (CD20- CD11c+ CD14- BDCA1+ CD11b+) were FACS purified from BDCA1+ magnetically. Neonatal monocytes (CD11c+ CD14+) and neonatal naive T cells (CD3+ CD4+ CD56- CD25- CD45RO-) were used as controls.

2018-09-21 | GSE104110 | GEO

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