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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE84686 | GEO | 2017/08/09

SECONDARY ACCESSION(S): PRJNA330840

REPOSITORIES: GEO

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Homo sapiens

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

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ena-DATASET-DIL-CAM-26-10-2017-13:09:14:723-445 - samples

Project description:By differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense. We also observed an IL-8–producing memory T cell subpopulation coexpressing CR1 and CR2 and with a gene expression signature resembling that of RTEs. JCI Insight. 2017;2(16):e93739. https://doi.org/10.1172/jci.insight.93739

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Relation between T CD4+: Regulatory cells and IL-2 producing cells

Project description:We previously proposed that lymphocyte homeostasis is achieved by a quorum-sensing like mechanism, based on the paracrine sensing of IL-2 by Foxp3(+) regulatory T CD4(+) cells. In turn, these cells will suppress IL-2 producing cells, thereby controlling the total number of T CD4(+) cells. As CD4(+) T regulatory cells are unable to produce IL-2, such control mechanism assumes the complete segregation of both lymphocyte subsets, that is to say they constitute distinct compartments. In the present study, we re-evaluate the above-described quorum-sensing mechanism by considering the non-exclusive possibility that a fraction of IL-2-producing cells might acquire regulatory function, implying the existence of a role for an autocrine sensing of IL-2 in the homeostasis of the regulatory compartment. According to the mouse models used in these experiments, RFP is used as a reporter for the Foxp3 expression. The transcription factor Foxp3 is the main hallmark of T CD4(+) regulatory cells. Therefore RFP(+) cells are associated to T CD4(+) regulatory cells. According to the mouse model, and our last publication (PMID: 24249704), the GFP is a reporter for cells that having activated the IL-2 locus within the last 2-3 weeks. This subset of cells is called IL-2p cells. 4 populations of conventional CD4+ T cell are analysed. 5 replicats for each.

2015-02-01 | E-GEOD-54686 | biostudies-arrayexpress

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Project description:IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation.

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Molecular and functional heterogeneity of IL-10-producing CD4+ T cells [Human 10x]

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ESBL-producing isolates from neonates in Tanzania

Project description:ESBL-producing isolates from neonates in Tanzania

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Molecular and functional heterogeneity of IL-10-producing CD4+ T cells [Mouse Bulk-seq]

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Molecular and functional heterogeneity of IL-10-producing CD4+ T cells [Mouse SMART-seq2]

2018-11-07 | GSE121386 | GEO

Transcriptome analysis of IFNγ producing and non-producing CD4 T cells during chronic intestinal inflammation.

Project description:Purpose: The goal of this study is to compare transcriptome profiles of IFNγ producing (Thy1.1+) and IFNγ non-producing (Thy1.1-) CD4 T cells during chronic intestinal inflammation using RNA sequencing. Methods: Total mRNA was isolated from FACS sorted CD44+Thy1.1+ and CD44+Thy1.1-CD4 T cells and sequenced in duplicate using Illumina HiSeq 2500 (2x100 base pair, paired-end reads). The sequence reads were aligned using mouse GRCm38.75 reference genome. DESeq2 software was used for differential expression analysis. Results: Differential expression analysis with DESeq2 algorithm revealed that a total of 942 and 1091 genes were significantly increased in the IFNγ+ and IFNγ- effector CD4 T cells, respectively (adjusted p value <0.05). We also performed gene set enrichment analysis (GSEA) by pre-ranking RNA sequencing data according to an adjusted p-value and the sign of differential expression. GSEA regults suggested that IFNγ+ CD4 T cells had terminally differentiated phenotype, while IFNγ- CD4 T cells had transcriptional profile associated with self-renewal and stemness. Conclusions: Our study suggests that effector CD4 T cells exist in a spectrum of differentiation status during chronic intestinal inflammation, which impacts pathogenicity of CD4 T cells.

2018-05-12 | GSE114346 | GEO

Regulatory T cells

Project description:Induced and activated regulatory CD4+ Foxp3+ cells compared Conventional naive CD4+ T cells were sorted and converted in vitro into adaptive Treg cells, activated Treg cells were generated in vitro from sorted Foxp3GFP+ cells

2012-01-18 | E-GEOD-28130 | biostudies-arrayexpress

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