Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neonatal CD8+ T cells resist terminal exhaustion during chronic infection [RNAseq_day30]

ABSTRACT: Chronic viral infections represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections (HIV, HCV), the underlying mechanisms remain poorly understood. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (LCMV clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially become effector cells early in chronic infection when compared to adult CD8+ T cells, and resist commitment to the exhausted differentiation trajectory. Further, neonatal CD8+ T cells are preferentially maintained as stem-like exhausted progenitors rather than terminally exhausted cells during the chronic phase of infection. The altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant, for the neonatal cells protect from viral replication. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influences key cell fate decisions during chronic infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE234303 | GEO | 2024/03/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neonatal CD8+ T cells resist terminal exhaustion during chronic infection [RNAseq_day8]

Project description:Chronic viral infections represent a major public health problem. Although it is well understood that neonates and adults respond differently to chronic viral infections (HIV, HCV), the underlying mechanisms remain poorly understood. In this study, we transferred neonatal and adult CD8+ T cells into a mouse model of chronic infection (LCMV clone 13) and dissected out the key cell-intrinsic differences that alter their ability to protect the host. Interestingly, we found that neonatal CD8+ T cells preferentially become effector cells early in chronic infection when compared to adult CD8+ T cells, and resist commitment to the exhausted differentiation trajectory. Further, neonatal CD8+ T cells are preferentially maintained as stem-like exhausted progenitors rather than terminally exhausted cells during the chronic phase of infection. The altered differentiation trajectories of neonatal and adult CD8+ T cells is functionally significant, for the neonatal cells protect from viral replication at the cost of early-onset immunopathology. Together, our work demonstrates how cell-intrinsic differences between neonatal and adult CD8+ T cells influences key cell fate decisions during chronic infection.

2024-03-07 | GSE234302 | 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

Transcription profiling by array of CD8 T cells from healthy individuals that express high levals of Programmed Death-1 protein

Project description:T cell dysfunction is an important feature of many chronic viral infections. In particular, it was shown that PD-1 regulates T cell dysfunction during chronic LCMV infection in mice and PD-1 high cells exhibit an intense exhausted gene signature. These findings were extended to human chronic infections such as HIV, HCV and HBV. However, it is not known if PD-1 high cells of healthy humans have the traits of exhausted cells. In this study, we provide a comprehensive description of phenotype, function and gene expression profiles of PD-1 high versus PD-1 low CD8 T cells in the peripheral blood of healthy human adults as following: 1) The percentage of naive and memory CD8 T cells varied widely in the peripheral blood cells of healthy humans and PD-1 was expressed by the memory CD8 T cells. 2) PD-1 high CD8 T cells in healthy humans did not significantly correlated with the PD-1 high exhausted gene signature of HIV specific human CD8 T cells or chronic LCMV specific CD8 T cells from mice. 3) PD-1 expression did not directly affect the ability of CD8 T cells to secrete cytokines in healthy adults. 4) PD-1 was expressed by the effector memory (TEM) compared to ‘terminally differentiated effector’ (TEMRA) CD8 T cells. 5) Finally, an interesting inverse relationship between CD45RA and PD-1 expression was observed. We used highly purified PD-1 high and PD-1 low from six healthy adult individuals and naive CD8 T cell populations from four of those individuals for gene expression studies

2011-01-11 | E-GEOD-26495 | biostudies-arrayexpress

ATAC-Seq profiling of progenitor exhausted and terminally exhausted CD8+ T-cells from tumors and chronic viral infection

Project description:Epigenetically similar subpopulations of exhausted CD8+ T-cells are found in chronic viral infection and tumors

2018-12-02 | GSE123236 | GEO

Bulk RNA-Seq profiling of progenitor exhausted (Slamf6+Tim-3-) and terminally exhausted (Slamf6-Tim-3+) CD8+ T-cells from tumors and chronic viral infection

Project description:Transcriptionally similar subpopulations of exhausted CD8+ T-cells are found in chronic viral infection and tumors

2018-12-02 | GSE123235 | GEO

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

2007-11-27 | GSE9650 | GEO

Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection

Project description:Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.

| EGAS00001004538 | EGA

dd195318-5103-4c2e-9845-d48e04787b77 - samples

| EGAD00001006259 | EGA

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).

2015-09-08 | E-GEOD-72752 | biostudies-arrayexpress

Defining memory-like CD8 T cells that respond to PD-1 therapy in chronic viral infection

Project description:Chronic viral infections are characterized by a state of CD8 T cell dysfunction termed exhaustion. A better understanding of the mechanisms that regulate CD8 T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8 T cells. Here we identify a novel population of virus-specific CD8 T cells with a T follicular helper (Tfh)-like signature in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These Tfh-like CD8 T cells expressed the programmed cell death-1 (PD-1) inhibitory receptor but at the same time also expressed co-stimulatory molecules and had a gene signature that was related to CD8 T cell memory precursor cells and hematopoietic stem cells (HSC). These Tfh-like CD8 T cells acted as stem cells during chronic infection undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells that were present in both lymphoid and non-lymphoid tissues. The Tfh-like CD8 T cells were found only in lymphoid tissues and resided predominantly in the T cell zones along with naÃ¯ve CD8 T cells. Interestingly, the proliferative burst after PD-1 blockade came almost exclusively from this Tfh-like CD8 T cell subset. Importantly, the transcription factor TCF1 played a cell intrinsic and essential role in the generation of Tfh-like CD8 T cells. Taken together, our study identifies Tfh-like CD8 T cells as the critical subset for maintaining the pool of virus-specific CD8 T cells during chronic infection and as the cells that proliferate after PD-1 blockade. These findings provide a better understanding of T cell exhaustion and have implications towards optimizing PD-1 directed immunotherapy. 8 samples isolated from CD8 T-cells in LCMV clone 13 GK1.5 infected mice (2 naÃ¯ve, 3 CXCR5+Tim3-, 3 CXCR5-Tim3+) cells were analyzed

2016-08-02 | E-GEOD-84105 | 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