Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE278803 | GEO | 2025/02/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single cell RNA sequencing of TCF-1+ P14 precursor cells sorted 3.25 days after infection with LCMV Armstrong [scRNA-Seq BD Rhapsody]

Project description:T-cell exhaustion limits effector T-cell function in chronic infection and tumors. The development of these hypofunctional T-cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T-cell populations in the early phase of acute infections. At that stage early developing TCF1+ precursor population shows an unexpected diversity, which includes precursors of normal memory T-cells but also cells with a phenotype, gene-expression, and epigenetic profile that resembles 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 precursor T-cells with at least two distinct phenotypes are preemptively generated irrespectively of the outcome of the infection. In this experiment, cells from day 3.25 pi were analyzed to determine if the different subsets could be detected.

2025-02-21 | GSE278805 | GEO

Single cell RNA sequencing of the progeny of PD1hi vs PD1low TCF-1+ P14 precursor cells on day 15 after secondary host infection with LCMV Armstrong [scRNA-Seq BD Rhapsody]

Project description:T-cell exhaustion limits effector T-cell function in chronic infection and tumors. The development of these hypofunctional T-cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T-cell populations in the early phase of acute infections. At that stage early developing TCF1+ precursor population shows an unexpected diversity, which includes precursors of normal memory T-cells but also cells with a phenotype, gene-expression, and epigenetic profile that resembles 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 precursor T-cells with at least two distinct phenotypes are preemptively generated irrespectively of the outcome of the infection. Here, using adoptively transferred P14 cells, these subsets were isolated early during infection, re-transfered into new hosts that were subsequently infected as well. The entire progeny of the re-transfered cells was analyzed on day 15 pi.

2025-02-21 | GSE278806 | GEO

Single cell RNA sequencing of TCF-1+ precursor cells reacting to LCMV gp33 vs np396 multimers sorted 30 days after infection with LCMV Armstrong [scRNA-Seq + TCR 10x]

Project description:T-cell exhaustion limits effector T-cell function in chronic infection and tumors. The development of these hypofunctional T-cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T-cell populations in the early phase of acute infections. At that stage early developing TCF1+ precursor population shows an unexpected diversity, which includes precursors of normal memory T-cells but also cells with a phenotype, gene-expression, and epigenetic profile that resembles 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 precursor T-cells with at least two distinct phenotypes are preemptively generated irrespectively of the outcome of the infection. In this experiment, the transcriptome and TCR-sequences of endogenous gp33 or np396 specific CD8 T-cells were analyzed on day 30 post infection to assess the role of TCR-affinity and antigen-specificity in the formation of the different CD8 T-cell precursors.

2025-02-21 | GSE278804 | GEO

Longitudinal expression data from CD8+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

Project description:During acute viral infections, naïve CD8+ T cells differentiate into effector CD8+ T cells and, after viral control, into memory CD8+ T cells. Memory CD8+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD8+ T cells become “exhausted” and have poor effector function, express multiple inhibitory receptors, possess low proliferative capacity, and cannot persist without antigen. To compare the development of functional memory T cells with poorly functional exhausted T cells, we generated longitudinal transcriptional profiles for each. Naive CD44Lo CD8+ T cells were isolated and sorted from uninfected C57BL/6 mice and H2-Db GP33-specific CD8+ T cells were sorted using MHC-I tetramers at d6, 8, 15, and 30 p.i. with either LCMV Arm or LCMV clone 13. RNA from these CD8+ T cells was processed, amplified, labeled, and hybridized to Affymetrix GeneChip MoGene 1.0 st microarrays

2012-11-23 | E-GEOD-41867 | biostudies-arrayexpress

Strength of CD28 costimulation directs self-renewal or differentiation of TCF-1+ PD-1+ CD8 T cells through metabolic regulation

Project description:During persistent antigen stimulation, such as in chronic infections and cancer, T cells differentiate into a hypofunctional exhausted state to survive. Exhausted PD-1+ CD8 T cell responses are sustained by TCF-1+ precursors (Tpex) that self-renew or differentiate into exhausted T cells (Tex) that retain some effector function. Tpex have high expression of the costimulatory molecule CD28 and are the cells that respond to PD-1 targeted immunotherapy. Here, we demonstrate that abrogation of CD28 signaling impairs maintenance of anti-viral T cell responses during chronic infection. Low-level CD28 signaling was required to preserve mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation. Our findings show that CD28 signaling is essential for long-term maintenance of antigen-specific T cells during chronic stimulation, and suggest that the activation status of antigen presenting cells determines Tpex differentiation into more functional effector-like Tex cells.

2023-07-01 | GSE200506 | GEO

Longitudinal expression data from CD8+ T cells responding to LCMV-Armstrong or LCMV-Clone 13

2012-11-23 | GSE41867 | GEO

RNA sequencing of human CD8+ T cell subsets [TEX]

Project description:RNA sequencing of human CD8+ T cell subsets to compare hypofunctional exhausted cells (TEX) to fully activated effector cells (TEFF).

2023-07-01 | GSE234100 | GEO

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