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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE278805 | GEO | 2025/02/21

REPOSITORIES: GEO

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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

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.

2025-02-21 | GSE278803 | 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.

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

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

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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

Prediction of broadly neutralizing antibodies [BD Rhapsody]

Project description:Prediction of broadly neutralizing antibodies [BD Rhapsody]

| PRJNA952998 | ENA

Early precursor T cells establish and propagate T cell exhaustion in chronic infection [ATAC-seq]

Project description:TCF1+ precursors of exhausted T cells maintain T cell immunity during chronic infection and cancer and mediate the response to immune checkpoint inhibition; however, their developmental requirements are poorly understood. Here, we demonstrate that high antigen load promoted the differentiation of TCF1+ precursor T cells, which acquired hallmarks of T cell exhaustion such as impaired production of IFN? within the first days after infection. Transcriptional profiling revealed that exhaustion was established first in precursor T cells while early effector cells retained a polyfunctional profile. Early precursor T cells exposed to high amounts of antigen showed epigenetic imprinting of T cell receptor-dependent transcription factor binding, were dependent on BACH2 and restricted to the generation of T cells displaying features of exhaustion. Overall, we demonstrate that T cell exhaustion manifests first in TCF1+ precursor T cells and is propagated subsequently to the pool of antigen-specific T cells.

2020-06-23 | GSE142575 | GEO

Early precursor T cells establish and propagate T cell exhaustion in chronic infection [RNA-seq]

Project description:TCF1+ precursors of exhausted T cells maintain T cell immunity during chronic infection and cancer and mediate the response to immune checkpoint inhibition; however, their developmental requirements are poorly understood. Here, we demonstrate that high antigen load promoted the differentiation of TCF1+ precursor T cells, which acquired hallmarks of T cell exhaustion such as impaired production of IFN within the first days after infection. Transcriptional profiling revealed that exhaustion was established first in precursor T cells while early effector cells retained a polyfunctional profile. Early precursor T cells exposed to high amounts of antigen showed epigenetic imprinting of T cell receptor-dependent transcription factor binding, were dependent on BACH2 and restricted to the generation of T cells displaying features of exhaustion. Overall, we demonstrate that T cell exhaustion manifests first in TCF1+ precursor T cells and is propagated subsequently to the pool of antigen-specific T cells.

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