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Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [WT vs KO +/- Tim3]

ABSTRACT: Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [WT vs KO +/- Tim3]

PROVIDER: PRJNA545703 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9165560.fastq.gz	Fastqsanger.gz
	SRR9165570.fastq.gz	Fastqsanger.gz
	SRR9165561.fastq.gz	Fastqsanger.gz
	SRR9165571.fastq.gz	Fastqsanger.gz
	SRR9165562.fastq.gz	Fastqsanger.gz

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Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [WT vs KO +/- Tim3]

Project description:Chronic CD8 T-cell stimulation in persisting infections or tumors can induce a stable gene expression program, known as T-cell dysfunction or exhaustion, that limits the cell’s effector functions and anti-viral and anti-tumor immunity. Thus far, the underlaying molecular mechanisms that induce and stabilize this phenotype are vaguely understood. We report here that establishing this program requires the thymocyte selection-associated high mobility group-box protein (Tox). Genetic disruption of Tox augments effector function, decreases the expression of PD-1, and significantly enhances immunopathology. These changes are linked to a failure in fixing the dysfunctional phenotype in the critical Tcf1+ progenitor population and to impaired epigenetic programing. Surprisingly, the gains in effector function co-incide with declining numbers of Tcf1+ cells and result ultimately in reduced total numbers of pathogen-specific T-cells. Thus, we establish Tox as a critical factor for the development of T-cell dysfunction and establish a clear link between CD8 T-cell intrinsic suppression of effector function and protection against immune-pathology.

2019-07-03 | GSE132033 | GEO

Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [KO vs WT Day 8]

Project description:Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [KO vs WT Day 8]

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Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [ToxKO vs WT Day 20]

Project description:Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [ToxKO vs WT Day 20]

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Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [ToxKO vs WT Day 20]

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Tox reinforces the phenotype and longevity of dysfunctional T cell populations during chronic viral infection [KO vs WT Day 8]

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Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection

Project description:Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection

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Project description:Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection [Bisulfite-Seq]

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Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection [ATAC-seq]