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The Heterogenicity of Virtual Memory CD8 T Cells in Relation to Their Cytokine Dependent Development

ABSTRACT: The Heterogenicity of Virtual Memory CD8 T Cells in Relation to Their Cytokine Dependent Development

PROVIDER: PRJNA1195109 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR31633823_1.fastq.gz	Fastqsanger.gz
	SRR31633823_2.fastq.gz	Fastqsanger.gz
	SRR31633825_1.fastq.gz	Fastqsanger.gz
	SRR31633825_2.fastq.gz	Fastqsanger.gz

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The Heterogenicity of Virtual Memory CD8 T Cells in Relation to Their Cytokine Dependent Development

Project description:The development of virtual memory CD8 T cells is dependent on IL-4, type I interferon, and IL-15. However, it remains unclear whether these cytokines individually contribute to the generation of specific subsets of virtual memory CD8 T cells. In this study, virtual memory CD8 T cells were categorized into four subsets based on Ly6C and Sca-1 expression, and their development was examined using knock-out mice lacking IFNAR1, IL-4, or IL-15Rα. Notably, both Ly6C+ Sca-1+ and Ly6C- Sca-1+ subsets were significantly reduced in the spleen of IFNAR1 knock-out mice, while the proportion of Ly6C+ Sca-1- VM CD8 T cells was reduced in IL-4-deficient mice. In IL-15Rα knock-out mice, both the Ly6C+ Sca-1- and Ly6C- Sca-1- subsets were significantly reduced. Bulk RNA sequencing analysis revealed distinct gene expression patterns in naïve cells, true memory cells, and four virtual memory cells subsets. Specifically, Ly6C+ subsets were enriched with IL-15 signal-related genes, whereas Ly6C- subsets and true memory cells were enriched for cell cycle-related genes. Functionally, the Ly6C+ subsets exhibited higher production of IFN-γ, TNF-α, and perforin compared to the Ly6C- subsets. Overall, this study demonstrates the heterogeneity of virtual memory CD8 T cells and highlights the cytokine-dependent nature for their development.

2024-12-12 | GSE283738 | GEO

Sm eggs Virtual memory T cells

Project description:Transcriptomics analysis of virtual memory CD8+ T cells after treatment with Schistosoma mansoni eggs.

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Characterization of CD8+ virtual memory T cells in IL-4 knockout mice using single-cell RNA sequencing

Project description:We profiled the heterogeneity of virtual memory T cells and observed changes in virtual memory T cell subsets under conditions of IL-4 deficiency in mouse spleens using single-cell RNA sequencing.

2024-08-14 | GSE274396 | GEO

Sm eggs Virtual memory T cells

Project description:Sm eggs Virtual memory T cells

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Virtual memory T-cells orchestrate extra-lymphoid responses conducive to resident memory

Project description:A primary immune response is typically initiated in secondary lymphoid organs. Virtual memory CD8+ T (TVM) cells are antigen-inexperienced T cells of a central-memory phenotype, acquired through self antigen-driven homeostatic proliferation. Unexpectedly, here we find that, TVM cells are composed of CCR2+ and CCR2- subsets that differentially elaborate a spectrum of effector- and memory-poised functions directly in the tissue. During a primary flu infection, TVM cells rapidly infiltrate the lung in the first day and execute early viral control. TVM cells that recognize viral antigen are retained in the tissue, clonally expand independent of secondary lymphoid organs, and preferentially give rise to tissue-resident memory cells. By orchestrating an extra-lymphoid primary response, heterogenous TVM cells bridge innate reaction and adaptive memory directly in the infected tissue.

2021-06-15 | GSE148364 | GEO

Analysis of gene-expression in normal, unmanipulated naïve (CD44lo/CD49dlo; CD5lo/CD5hi) and Virtual memory (CD44hi/CD49dlo) T cells

Project description:Splenocytes from lymphoreplete, unmanipulated mice were analyzed for basal mRNA levels. We hypothesized, based on previous data from our lab and others, that many cytokine/inflammatory response genes would show an increase from naïve CD5lo<CD5hi<Virtual memory.

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Transcription profiling of human CD8 naive (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells

Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.

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Project description:Transcriptomic data linked to our study showing that DOCK2 sets the threshold for entry into the virtual memory CD8+ T cell compartment by negatively regulating tonic TCR triggering

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Generation of virtual memory from relatively highly self-reactive is a mechanism of self-tolerance

Project description:Virtual memory T cell show an intermediate expression profile in between naïve and true memory T cells. Most plausible explanation is that they trigger partial memory differentiation program.

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A distinct CD8+ T cell subset derived from virtual memory T cells causes alopecia areata through innate-like cytotoxicity [RNA-seq]

Project description:Virtual memory T (TVM) cells are a T-cell subtype that exhibit a memory phenotype without prior exposure to a foreign antigen. Although several recent studies suggest that TVM cells exert anti-viral and anti-bacterial function, pathological roles of TVM cells causing inflammatory diseases have not been studied. Here, we identified a novel CD8+ T-cell subset (CD44s-hiCD49dlo CD8+ T cells), which is originated from TVM cells and can cause a chronic inflammatory disease, alopecia areata (AA). In the skin of alopecic mice, we detected a distinct TVM-cell subpopulation characterized by superior expression of CD44 and features of tissue residency, which was transcriptionally, phenotypically, and functionally distinct from conventional CD8+ TVM cells. Mechanistically, this cell population could be induced from conventional TVM cells by IL-12, IL-15, and IL-18 stimulation. Moreover, the pathological activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-depedent innate-like cytotoxicity against target cells, which was further augmented by IL-15 stimulation and triggered the onset of disease. Collectively, our results suggest a new immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity.

2023-05-16 | GSE229145 | GEO

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