Similar Datasets
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
Project description:Effect of HPK1 inhibitor on exhausted CD8 T cells
| PRJNA906090 | ENA
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.
2015-09-08 | GSE72752 | GEO
Project description:We aimed to investigate the association between HPK1 expression and exhausted status of tumor.
2023-09-01 | GSE220795 | GEO
Project description:Transcriptional study of four defiined CD8 Tcell subset to understand the mechanism of exhaustion hierarchy
2020-05-11 | GSE149876 | GEO
Project description:Open chromatin accessibility analysis of four defiined CD8 Tcell subsets to understand the mechanism of exhaustion hierarchy
2020-05-11 | GSE149877 | GEO
Project description:To identify the role of KLF4 on exhausted CD8 T-cells, we retrovirally transduced Klf4 into OT-I CD8 T-cells on day1 of in vitro exhaustion model and repeatedly treated OVA peptide to induce exhaustion. Then we analyzed the gene expression profiles of these transduced cells by RNA-sequencing.
2022-10-24 | GSE212804 | GEO
Project description:In this study, we examined the role of the transcriptional regulator EGR2 in CD8+ T cell exhaustion during chronic viral infection. Flow cytometric analysis indicated that EGR2 deficient CD8+ T cells had a block in differentiation and failed to undergo terminal exhaustion. To confirm this at a whole transcriptome level, we conducted RNAseq analysis on sorted splenic virus-specific tetramer+ CD8+ T cells isolated at day 20 post-infection with chronic LCMV-Cl13 from either littermate control or EGR2 T cell conditional knock-out mice. The resulting data demonstrated that there was a global loss of the terminally exhausted gene signature within EGR2 KO CD8+ T cells. This suggests that EGR2 promotes terminal CD8+ T cell exhaustion.
2021-03-02 | GSE134689 | GEO
Project description:In this study, we examined the role of the transcriptional regulator EGR2 in CD8+ T cell exhaustion during chronic viral infection. Flow cytometric and RNAseq analysis indicated that EGR2 deficient CD8+ T cells had a block in differentiation and failed to undergo terminal exhaustion. To examine the direct gene targets of EGR2 during exhaustion, we conducted ChIPseq analysis on enriched bulk splenic CD8+ T cells isolated at day 20 post-infection with chronic LCMV-Cl13 from C57BL/6J mice. The resulting data demonstrated that EGR2 directly controls expression of key gene targets, including Pdcd1, Tigit, Cxcr5, Tcf7, Bach2 and Bcl6.
2021-03-02 | GSE134708 | GEO
Project description:We then investigated how HPK1 induces new changes by comparing the open chromatin regions (OCRs) with WT control and founded that the ATAC-seq tracks were aligned with the previously reported OCRs of exhausted . HPK1 knockout induced loss of peaks in loci enriched in exhausted T (Tex) cells (e.g., PD-1, TIM-3, LAG-3, and TOX locus), indicating that HPK1 knockout could overcome some negative effects caused by TME, ameliorate T cell exhaustion and thus extend their effector function (Figure S2F). Moreover, we also found that more accessible regions in HPK1-knockout CD8+TILs showed significant enrichment for pathways associated with cell cycle, antigen processing and presentation, T cell receptor signaling, Glyoxylate and dicarboxylate metabolism, AMPK pathway, and C-type lectin receptor signaling pathway (Figure S2G). It has been demonstrated that many peak changes were unique to either the early dysfunctional or functional state and included TCR signaling and cytokine production pathway genes. Pauken and the colleagues identified two metagenes in anti-PD-L1–treated exhausted T cell (TEX) compared to control TEX; one corresponding to leukocyte activation and one to cell cycle. The anti-PD-L1–treated TEX metagenes displayed some overlap with effector T cells (TEFF), largely driven by cell cycle pathways, but minimal overlap with Memory T cell (TMEM). Thus, we concluded that HPK1-/- TILs are prone to be effort T cells defined according to the chromatin states.
2020-05-16 | GSE150635 | GEO