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Precursors of exhausted T-cells are preemptively formed in acute infection

ABSTRACT: Precursors of exhausted T-cells are preemptively formed in acute infection

PROVIDER: PRJNA1168953 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30887100.fastq.gz	Fastqsanger.gz
	SRR30887500.fastq.gz	Fastqsanger.gz
	SRR30887101.fastq.gz	Fastqsanger.gz
	SRR30887501.fastq.gz	Fastqsanger.gz
	SRR30887102.fastq.gz	Fastqsanger.gz

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Transcription profiling of mouse naive, effector, memory and exhausted virus-specific CD8 T cells after chronic viral infection

Project description:CD8 T cells normally differentiate from resting naÃ¯ve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Experiment Overall Design: Three or four independent samples were sorted by flow cytometry for each cell type (naive, effector, memory and exhausted) virus-specific CD8 T cells. RNA was extracted and hybridized to Affymetrix microarrays.

2008-06-16 | E-GEOD-9650 | biostudies-arrayexpress

Precursors of exhausted T-cells are preemptively formed in acute infection

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-02-21 | GSE278807 | GEO

Bulk RNA sequencing of PD1hi vs PD1low TCF-1+ P14 precursor cells sorted 7 days after infection with LCMV Armstrong [bulk RNA-seq]

Project description:T-cell exhaustion limits effector T-cell function in chronic infection and tumors. The development of these hypofunctional T-cells was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found strong diversity among precursor T-cells formed early in acute infections. This includes precursors of normal memory T-cells and cells with phenotypes, gene-expression, and epigenetic profiles that resemble precursors of exhausted T-cells found in chronic infections. We demonstrate that high ligand affinity promotes, and PD-1 signaling restricts the development of these precursors. While these exhausted precursors are initially frequently found, they decline without being completely lost in infections the immune system resolves. We therefore concluded that T-cells are preemptively generated irrespectively of the outcome of the infection.

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Chronic viral infection of naive, effector, memory and exhausted virus-specific CD8 T cells

Project description:CD8 T cells normally differentiate from resting naïve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Keywords: infection response

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CD39 expression identifies terminally exhausted CD8+ T cells

Project description:Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. CD8+ T cells from subjects with HCV infection were sorted and pelleted and re-suspended in TRIzol (Invitrogen). RNA extraction was performed using the RNAdvance Tissue Isolation kit (Agencourt). Concentrations of total RNA were determined with a Nanodrop spectrophotometer or Ribogreen RNA quantification kits (Molecular Probes/Invitrogen). RNA purity was determined by Bioanalyzer 2100 traces (Agilent Technologies). Total RNA was amplified with the WT-Ovation Pico RNA Amplification system (NuGEN) according to the manufacturer's instructions. After fragmentation and biotinylation, cDNA was hybridized to HG-U133A 2.0 microarrays (Affymetrix).

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