Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Memory-like CD8 T-cells sustain the immune response to chronic viral infections.

ABSTRACT: We have discovered a small subpopulation of virus-specific CD8 T-cells that sustains the T-cell response in chronic infections. These cells are defined by - and depend on - the expression of the transcription factor Tcf1 (T cell factor 1) and show key characteristics of central memory cells while lacking an effector signature. Unlike conventional memory cells, Tcf1+ T-cells display hallmarks of an “exhausted” phenotype, including the expression of certain inhibitory receptors.

ORGANISM(S): Mus musculus

PROVIDER: GSE83978 | GEO | 2016/08/22

SECONDARY ACCESSION(S): PRJNA327590

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Memory-like CD8 T-cells sustain the immune response to chronic viral infections.

Project description:We have discovered a small subpopulation of virus-specific CD8 T-cells that sustains the T-cell response in chronic infections. These cells are defined by - and depend on - the expression of the transcription factor Tcf1 (T cell factor 1) and show key characteristics of central memory cells while lacking an effector signature. Unlike conventional memory cells, Tcf1+ T-cells display hallmarks of an âexhaustedâ phenotype, including the expression of certain inhibitory receptors. Naive Tcf1-GFP+ P14 cells (Naive) were transferred into Vb5 recipient mice (CD45.1) prior to infection with LCMV clone 13 (c13). Tcf1-GFP+ P14 cells (chronic Tcf1+) and Tcf1-GFP- P14 cells (chronic Tcf1-) were flow sorted on day 28 post infection. Naive Tcf1-GFP+ P14 cells (Naive) were also transferred into C57BL/6 hosts (CD45.1.2) prior to infection with LCMV Armstrong (Arm). Tcf1-GFP+ P14 cells (memory Tcf1+) and Tcf1-GFP- P14 cells (memory Tcf1-) were flow sorted on day 28 post infection. Total RNA was extracted, cDNA libraries prepared and sequencing was performed using Illumina HiSeq 2500 technology.

2016-08-22 | E-GEOD-83978 | biostudies-arrayexpress

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [ATAC-seq]

Project description:The goal of this study is to determine the capacity of Tcf1 to reprogram exhausted CD8+ T cells for function restoration. Tex cells elicited by chronic infection contain a CXCR5+Tim3– subset that has stem cell-like self-renewing capacity and expresses an elevated level of Tcf1 (termed Tex-stem), and Tex-stem cells depend on Tcf1 for generation and persistence. We show that ectopic Tcf1 expression profoundly affected the chromatin accessibility of Tex cells.

2020-04-30 | GSE139024 | GEO

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [RNA-seq]

2020-04-30 | GSE139057 | GEO

Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [CUT&RUN]

2020-04-30 | GSE139056 | GEO

Tumor-resident memory-like CD8 T cells represent an essential cellular target for cancer immunotherapy

Project description:Persistent exposure to high levels of antigen results in the progressive exhaustion of T cells and has been thought to preclude the formation of memory. In contrast to the latter assumption, we show here that tumor-specific CD8 T cells residing in the tumor microenvironment include a Tcf1 expressing sub population that has key characteristics of central memory cells, lack an effector cell signature but display hallmarks of exhausted T cells, including the expression co-inhibitory receptors such as PD1. Similar memory-like cells are identified in melanoma patients. Preclinical mouse models reveal that the expansion of tumor-specific CD8 T cells, the production of terminally differentiated exhausted CD8 T cells and sustained tumor control in response to therapeutic vaccination or immune checkpoint blockade critically depends on the presence of these memory-like CD8 T cells. Tumor immune responses thus harbor tumor resident memory-like CD8 T cell populations, which can be therapeutically targeted to improve immune control of cancer.

2019-01-10 | GSE114631 | GEO

RNA Polymerase II Pausing Factor NELF in CD8+ T Cells Promotes Anti-Tumor Immunity

Project description:The master transcriptional regulator T cell factor 1 (TCF1) is required for the anti-tumor functions of memory and stem-like CD8+ T cells. However, how TCF1 partners with other transcription factors to orchestrate the gene activation program critical for anti-tumor immunity remains poorly understood. Here we show that negative elongation factor B (NELFB), an RNA polymerase II pausing factor, cooperates with TCF1 in T cell responses to cancer. Genetic ablation of mouse Nelfb in mature T lymphocytes severely impaired anti-tumor immunity responding to both primary tumor challenge and tumor antigen-mediated vaccination. NELFB depletion resulted in more exhausted, and reduced memory, T cell populations, whereas its ectopic expression boosted host anti-tumor immunity and efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy. Mechanistically, NELFB is physically associated with TCF1 and recruited preferentially to TCF1-enriched transcriptional enhancers and promoters in CD8+ T cells. Nelfb ablation significantly restricted chromatin accessibility to these TCF1-associated loci. Thus, NELFB is a previously unrecognized functional partner of TCF1 that potentiates the chromatin openness of TCF1-targeting regulatory elements. Our findings also suggest that augmenting NELFB expression in CD8+ T cells may improve therapeutic outcomes of anti-cancer CAR-T immunotherapies.

2022-03-19 | GSE182862 | 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.

2020-08-28 | GSE142686 | GEO

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

10X single-cell RNASeq profiling of tumor-infiltrating CD8+ T-cells from B16-OVA mouse melanoma tumors

Project description:Distinct populations of progenitor exhausted (Tcf1+Tim-3-) and terminally exhausted (Tcf1-Tim-3+) CD8+ T-cells occur in B16-OVA tumors

2018-11-20 | GSE122675 | 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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data