Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel lymphocytic choriomeningitis virus strain sustains abundant exhausted progenitor CD8 T cells without systemic viremia

ABSTRACT: Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and a natural mouse pathogen. LCMV Armstrong, an acutely resolved strain, and LCMV Clone 13, a mutant that establishes chronic infection, have provided contrasting infection models that continue to inform the fundamental biology of T cell differentiation, regulation of exhaustion, and response to checkpoint blockade. Here, we report the isolation and characterization of LCMV Minnesota (LCMV-MN), which was naturally transmitted to laboratory mice upon cohousing with pet shop mice and shares 80-95% amino acid homology with previously characterized LCMV strains. Infection of laboratory mice with purified LCMV-MN resulted in viral persistence that was intermediate between LCMV Armstrong and Clone 13, with widely disseminated viral replication and viremia that was controlled within 15-30 days, unless CD4 T cells were depleted prior to infection. LCMV-MN responding CD8+ T cells biased differentiation towards the recently described PD1+ CXCR5+ Tim-3lo stem-like CD8+ T cell population (also referred to as T exhausted progenitors, Tpex) that effectuates responses to PD-1 blockade checkpoint inhibition, a therapy that rejuvenates responses against chronic infections and cancer. This subset resembled previously characterized PD1+ TCF1+ stem-like CD8+ T cells by transcriptional, phenotypic, and functional assays, yet was atypically abundant. LCMV-MN may provide a tool to better understand the breadth of immune responses in different settings of chronic antigen stimulation as well as the ontogeny of T exhausted progenitors and the regulation of responsiveness to PD-1 blockade.

ORGANISM(S): Mus musculus

PROVIDER: GSE207983 | GEO | 2022/08/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Whole mouse genome analysis of LCMV-specific CD4 and CD8 T cells throughout acute and chronic LCMV infection.

Project description:CD4 and CD8 T cells display functional defects during chronic infection such as loss of certain cytokines. Recent studies have suggested that CD4 T cells may actually gain other functions, however. Here, we analyzed gene expression profiles from LCMV-specific CD4 and CD8 T cells throughout the response to either acute LCMV or chronic LCMV infection. This alllowed us to identify CD4-specific changes during chronic infection compared to acute infection but also revealed shared core regulators between CD4 and CD8 T cells. LCMV-specific CD4 and CD8 T cells were isolated 6, 8, 15 and 30 days post infection with LCMV Armstrong or LCMV clone 13. Naïve CD4 and CD8 T cells were also isolated from naïve mice as comparisons. Four replicates of each sample were hybridized. The only exception is LCMV-specific CD4 T cells isolated 6 days post infection with LCMV-Arm where only three replicates were hybridized.

2012-12-12 | E-GEOD-30431 | biostudies-arrayexpress

10X single-cell RNASeq profiling of GP33-tetramer+ CD8+ T-cells from mice chronically infected with LCMV Clone 13

Project description:Four distinct populations of exhausted CD8+ T-cells occur in chronic LCMV Clone 13 infection

2018-11-20 | GSE122712 | GEO

Longitudinal single cell transcriptional and epigenetic mapping of effector, memory, and exhausted CD8 T cells reveals shared biological circuits across distinct cell fates [scRNA-Seq]

Project description:Longitudinal scRNA-seq from LCMV-specific P14 CD8 T cells in LCMV-Armstrong and LCMV-Clone 13 infection

2022-10-31 | GSE199563 | GEO

Longitudinal single cell transcriptional and epigenetic mapping of effector, memory, and exhausted CD8 T cells reveals shared biological circuits across distinct cell fates [scATAC-Seq 2]

Project description:Longitudinal scATAC-seq from LCMV-specific P14 CD8 T cells in LCMV-Armstrong and LCMV-Clone 13 infection

2022-10-31 | GSE199557 | GEO

Longitudinal single cell transcriptional and epigenetic mapping of effector, memory, and exhausted CD8 T cells reveals shared biological circuits across distinct cell fates [scRNA-seq and scATAC-seq coAssay]

Project description:Longitudinal scRNA-seq and scATAC-seq from LCMV-specific P14 CD8 T cells in LCMV-Armstrong and LCMV-Clone 13 infection

2023-05-31 | GSE230363 | GEO

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

Changes in chromatin accessibility assocaiated with CD8 T cell responses to viral infections

Project description:The goal of this study was to identify the molecular programming using ATAC-seq of CD8 T cells responding to different viral infections. Mice were infected with either LCMV Armstrong to model an acute infection or LCMV Clone-13 to model a chronic infection. At various time points following infection, virus-specific CD8 T cells were purified and ATAC-seq performed. These data identify the changes in chromatin accessibility associated with acute infections and the establishment of functional memory versus those accessibility changes associated with chronic infection.

2017-01-31 | GSE83081 | GEO

Gene expression profiles at the single cell level of CD8+ T cells from the spleens of LCMV-Armstrong or LCMV-Clone 13 infected mice

Project description:The transcriptomes of CD8+ T cells from LCMV-Armstrong and LCMV-Clone 13 infected mice are known to be distinct from one another. We used single cell RNA sequencing (scRNA-seq) to analyze the transcriptomic diversity of splenic CD8+ T cells in these two infection conditions at various timepoints after infection.

2023-01-04 | GSE213470 | GEO

Gene expression profile analysis of mouse whole spleen following infection by lymphocytic choriomeningitis virus (LCMV), comparing LCMV-Armstrong and LCMV-Clone 13 expression patterns at 0, 5, 9, and 30 days

Project description:To identify mechanisms behind immunosuppression during virus infections, we infected mice with LCMV-Armstrong and LCMV-Clone 13 expression patterns. LCMV-Armstrong induces a T-cell reaction that resolves infection within 8-10 days, while LCMV-Clone13 generates a persisten infection through immunosuppression. We used microarray to uncover splenic gene expression patterns specific to each LCMV infection at 5, 9, and 30 days C57BL6 mice, 6-10 weeks old, were infected with LCMV-Armstrong and LCMV-Clone 13 or left uninfected (naïve). At days 5, 9, and 30 whole spleens were harvested for RNA extraction and hybridization on Affymetric microarray.

2013-02-15 | E-GEOD-44322 | biostudies-arrayexpress

Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment

Project description:Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute/chronic infectious diseases and in the tumor microenvironment remains unclear. We recently demonstrated that IFN-a/b receptor (IFNAR) signaling promotes Treg function in autoimmunity. Here, we dissected the functional role of IFNAR-signaling in Tregs using Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice in acute LCMV Armstrong, chronic LCMV Clone-13 infection, and in a transplantable colon adenocarcinoma model. In both viral and tumor models, IFNARfl/flxFoxp3YFP-Cre mice Tregs expressed enhanced Treg associated activation antigens. The enhanced activated phenotype was also seen when we compared the transcriptomes of IFNARfl/flxFoxp3YFP-Cre mice Tregs with the wild type (WT) Tregs by RNA-Seq on day 5 Armstrong and day 25-post Clone-13 infection. LCMV-specific CD8+ T cells and tumor infiltrating lymphocytes from IFNARfl/flxFoxp3YFP-Cre mice produced less antiviral and antitumor IFN-g and TNF-a. In the chronic infection model, the numbers of antiviral effector and memory CD8+ T cells were decreased in IFNARfl/flxFoxp3YFP-Cre mice and the effector CD4+ and CD8+ T cells exhibited a phenotype compatible with enhanced exhaustion. IFNARfl/flxFoxp3YFP-Cre mice cleared Armstrong infection normally, but had higher viral titers in sera, kidneys and lungs during chronic infection, and a higher tumor burden than the WT controls. Thus, type I IFN signaling in Tregs is context-dependent, resulting in enhanced suppressor function in some models of autoimmunity, but decreased suppressor function in acute/chronic viral infection and in the tumor microenvironment.

2017-10-24 | GSE104507 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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