An early precursor CD8 T cell that adapts to acute or chronic viral infection [bulk RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1196833 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31687300_1.fastq.gz | Fastqsanger.gz | |||
| SRR31687300_2.fastq.gz | Fastqsanger.gz | |||
| SRR31687301_1.fastq.gz | Fastqsanger.gz | |||
| SRR31687301_2.fastq.gz | Fastqsanger.gz | |||
| SRR31687302_1.fastq.gz | Fastqsanger.gz |
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Project description:An early precursor CD8 T cell that adapts to acute or chronic viral infection [scRNA-seq]
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Project description:This study examines the origin and differentiation of stem-like CD8+ T cells that are essential for sustained T cell immunity in chronic viral infections and cancer and also play a key role in PD-1 directed immunotherapy. These PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells, also referred to as precursors of exhausted T cells, have a distinct program that allows them to adapt to chronic antigen stimulation. Using the mouse model of chronic LCMV infection we found that virus specific stem-like CD8+ T cells are generated early (day 5) during chronic infection suggesting that this crucial fate commitment occurs irrespective of infection outcome. Indeed, we found that nearly identical populations of stem-like CD8+ T cells were generated early after acute or chronic LCMV infection and that antigen was essential for maintaining the stem-like phenotype. We next performed reciprocal adoptive transfer experiments to determine the fate of these early stem-like CD8+ T cells after viral clearance versus persistence. Following transfer of day 5 stem-like CD8+ T cells from chronically infected into acutely infected mice, these cells downregulated canonical markers of the chronic stem-like CD8+ T cells and expressed markers (CD127 and CD62L) associated with central memory CD8+ T cells. Reciprocally, when day 5 stem-like cells from acutely infected mice were transferred into chronically infected mice these CD8+ T cells functioned like chronic resource cells and responded effectively to PD-1 therapy. These findings highlight the ability of these early PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells to adapt their differentiation trajectory to either an acute or chronic viral infection. Most importantly, our study shows that the host is prepared a priori to deal with a potential chronic infection.
2025-01-11 | GSE284012 | GEO
Project description:This study examines the origin and differentiation of stem-like CD8+ T cells that are essential for sustained T cell immunity in chronic viral infections and cancer and also play a key role in PD-1 directed immunotherapy. These PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells, also referred to as precursors of exhausted T cells, have a distinct program that allows them to adapt to chronic antigen stimulation. Using the mouse model of chronic LCMV infection we found that virus specific stem-like CD8+ T cells are generated early (day 5) during chronic infection suggesting that this crucial fate commitment occurs irrespective of infection outcome. Indeed, we found that nearly identical populations of stem-like CD8+ T cells were generated early after acute or chronic LCMV infection and that antigen was essential for maintaining the stem-like phenotype. We next performed reciprocal adoptive transfer experiments to determine the fate of these early stem-like CD8+ T cells after viral clearance versus persistence. Following transfer of day 5 stem-like CD8+ T cells from chronically infected into acutely infected mice, these cells downregulated canonical markers of the chronic stem-like CD8+ T cells and expressed markers (CD127 and CD62L) associated with central memory CD8+ T cells. Reciprocally, when day 5 stem-like cells from acutely infected mice were transferred into chronically infected mice these CD8+ T cells functioned like chronic resource cells and responded effectively to PD-1 therapy. These findings highlight the ability of these early PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells to adapt their differentiation trajectory to either an acute or chronic viral infection. Most importantly, our study shows that the host is prepared a priori to deal with a potential chronic infection.
2025-01-11 | GSE284013 | GEO
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 naïve 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 naïve, 3 CXCR5+Tim3-, 3 CXCR5-Tim3+) cells were analyzed
2016-08-02 | E-GEOD-84105 | biostudies-arrayexpress
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 naïve 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.
2016-08-02 | GSE84105 | GEO
Project description:Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection
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Project description:Purpose: To characterize the tumor-specific TRM cells in LNs, skin, lung and liver in mice with melanoma-associated vitiligo (MAV). Bulk RNA-seq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics. Methods: CD8+THy1.1+ T cells were sorted from DLN, skin lung and liver of MAV mice and bulk RNA-sequenced Results: Heterogenouse CD8 memory populations with both circulatating and resident phenotypes were identified. Conclusions: Tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.
2021-07-04 | GSE169237 | GEO
Project description:Lysine deacetylase inhibitors (KDACi) show immunomodulatory properties, promoting differntiation of an IL7RhiPD1lo memory precursor (MPEC) phenotype on polyclonal stimulation in vitro and enhancing functional memory responses during infection or immunisation in vivo. We isolated (MACS positive selection) primary human CD8+ T cells from healthy blood donors and treated them for 6 days with low dose sodium valproate (5mM, d0) with concurrent stimulation with anti-CD2/3/28 microbeads, then undertook bulk ATACseq of lysed cells.
2024-09-01 | E-MTAB-13367 | biostudies-arrayexpress
Project description:Lysine deacetylase inhibitors (KDACi) show immunomodulatory properties, promoting differentiation of an IL7RhiPD1lo memory precursor (MPEC) phenotype on polyclonal stimulation in vitro and enhancing functional memory responses during infection or immunisation in vivo. We isolated (MACS positive selection) primary human CD8+ T cells from healthy blood donors and treated them for 6 days with low dose sodium valproate (5mM, d0) with concurrent stimulation with anti-CD2/3/28 microbeads, then undertook bulk RNAseq of lysed cells.
2024-09-01 | E-MTAB-13366 | biostudies-arrayexpress