Inflammation durably imprints memory CD4+ T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA974831 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Memory CD4 T cells are critical to human immunity, yet it is unclear if viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)-specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly two years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely due to a chromatin accessibility landscape altered by inflammation. Moreover, S-specific CD4 T cells primed by infection had reduced proliferative capacity in vitro relative to vaccine-primed cells. Furthermore, the transcriptional state of S-specific memory CD4 T cells was minimally altered by booster immunization and/or breakthrough infection. Thus, these data demonstrate the durable imprint of inflammation on CD4 T cell memory which affected function and may have consequences for long-term immunity.
2024-03-15 | GSE233046 | GEO
Project description:CD4 T cells play critical roles in promoting inflammation and helping immune responses, but knowledge of how memory CD4 T cells are regulated and how they help adaptive immune responses is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naïve CD4 T cells undergo substantial expansion following viral infection, but can induce lethal TH1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper (Tfh) cell subsets that correlate with improved adaptive responses and minimal tissue damage following viral infection. Importantly, our analyses revealed that type I interferon regulates the expansion of naïve CD4 T cells, but does not seem to play a critical role in regulating the expansion of memory CD4 T cells. Moreover, blockade of type I interferon signaling abrogated lethal CD4 T cell inflammation following viral infection. Taken together, these data demonstrate a previously undescribed function for memory CD4 T cells: to help adaptive immunity with minimal harm to the host. These findings are important for rational vaccine design and for improving the safety and efficacy of adoptive T cell therapies against persistent antigens. Primary and memory SMARTA cells were MACS-purified by negative selection (STEMCELL) and then FACS-sorted to 98% purity on a FACS Aria (BD Biosciences) according to congenic marker expression (CD45.1+ for secondary, and CD45.1+ CD45.2+ for primary, CD4 T cell responses).
2017-03-31 | GSE92474 | GEO
Project description:TNIK signaling imprints CD8+ T memory formation early after priming
| PRJNA525144 | ENA
Project description:Heterogenity of memory CD4 T cells
| PRJNA910478 | ENA
Project description:Single-cell analyses of memory CD4 T cells after LCMV Armstrong infection and memory-phenotype CD4 T cells
2022-05-16 | GSE145999 | GEO
Project description:IFN -YFP reporter mice (Jax# 017580) were immunized intravenously with attenuated Salmonella enterica serovar Typhimurium intravenously. 45 days later, tissue resident memory CD4 T cells (CD69+ YFP+) in the liver, effector memory CD4 T cells (CD69- YFP+) in the liver, and effector memory CD4 T cells (CD69- YFP+) in the spleeen were sorted and RNA was sequenced
2022-09-17 | GSE211181 | GEO
Project description:Transgenerational inheritance of acquired memory and epigenetic imprints through maternal gametes
| PRJNA574403 | ENA
Project description:Transgenerational inheritance of acquired traits/characteristics from ancestors is believed to play important roles in evolution, as well as health problems/symptoms not due to “classical genetic inheritance”. However, the central enigma, such as how the acquired transgenerational characteristics are developed, and how the acquired traits are transmitted from generations to generations of offspring, largely remained veiled. In this study, we used C elegans as a model system and provide evidence that the dynamic of H3K27me3 as a hallmark and regulator for the gut-mediated transgenerational inheritance of acquired traits. Further, we demonstrate that yolk proteins guide the establishment of the acquired epigenetic imprints in soma, as well as determines the transgenerational inheritance of epigenetic imprints and subsequent acquired behavior in offspring by maternal provision. Taken together, our findings support that yolk proteins both function as a systemic “non-nuclear factor” for establishing the somatic epigenetic imprints and as a “cargo” to transmit acquired epigenetic information to the subsequent generations through oocytes.
2022-09-10 | GSE138059 | GEO
Project description:Using an experimental model of graft versus host disease (GVHD) to examine T cell-mediated inflammation within the colon, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin, CD11c, has a biased central memory phenotype and memory T cell transcriptional profile, possesses innate-like properties by gene expression analysis, and has increased expression of the gut-homing molecules, α4β7 and CCR9. Using a number of complementary GVHD mouse models, we show that adoptive transfer of these cells results in TH1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality due to early accumulation of these cells in the GI tract. The pathogenic effects of this CD4+ T cell population was critically dependent upon co-expression of the IL-23 receptor which was required for maximal inflammatory effects. Colonic inflammation was regulated by IL-10 that was produced by non-Foxp3-expressing CD4+ T cells which attenuated lethality in the absence of functional CD4+ Foxp3+ T cells. Thus, coordinate expression of CD11c and the IL-23R defines a novel IL-10 regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers as occurs in GVHD as well as other immune-mediated inflammatory bowel disorders.
2016-08-12 | GSE83552 | GEO
Project description:Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) of naïve/ effector (D6)/ memory (D80) p14 T cell [wild-type (WT) and Tnik-/- (KO)] isolated form spleen of naïve or adoptively transferred and LCMV-WE immunized mice. Methods: Transcriptomic profiles of splenic naïve wild-type (WT) and Tnik-/- (KO) p14 T cells (8-week-old mice) or splenic effector (D6) and memory (D80) p14 T cells (post adoptive transfer and LCMV-WE immunization) were assessed in duplicates or triplicate by deep sequencing, using Illumina HiSeq 2500. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: We mapped about 30 million sequence reads per sample to the mouse genome (GRCm38 - mm10) and identified expressed transcripts in splenic WT and Tnik−/− p14 T cells. RNA-seq data confirmed stable expression of known housekeeping genes. Differentially expressed genes between the WT and Tnik−/− p14 T cells from naïve, D6 or D80 were identified with a fold change ≥1.5 and p-value <0.05. Hierarchical clustering and gene ontology analysis of differentially expressed genes uncovered genes that may contribute to regulation of stemness, transcriptional regulation, cell cycle regulation, survival and function of T cells. Conclusions: Our study represents the first detailed transcriptome analysis of WT versus Tnik-/- p14 T cells in the context of acute viral infection, with biologic replicates, generated by RNA-seq technology. Our results show that TNIK regulates T cell fate. Evaluation of mRNA content in effector (D6) and memory (D80) p14 T cells revealed that TNIK-deficiency during T cell activation enhances proliferation, terminal differentiation and glycolysis of effector T cells, while compromising steady-state metabolic activity of memory T cells. We conclude that TNIK imprints memory formation early after CD8+ T cell priming.
2020-02-24 | GSE127734 | GEO