GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE131642 Query DataSets for GSE131642
Status Public on Jul 03, 2019
Title Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection [Bisulfite-Seq]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary Chronic CD8 T-cell stimulation in persisting infections or tumors can induce a stable gene expression program, known as T-cell dysfunction or exhaustion, that limits the cell’s effector functions and anti-viral and anti-tumor immunity. Thus far, the underlaying molecular mechanisms that induce and stabilize this phenotype are vaguely understood. We report here that establishing this program requires the thymocyte selection-associated high mobility group-box protein (Tox). Genetic disruption of Tox augments effector function, decreases the expression of PD-1, and significantly enhances immunopathology. These changes are linked to a failure in fixing the dysfunctional phenotype in the critical Tcf1+ progenitor population and to impaired epigenetic programing. Surprisingly, the gains in effector function co-incide with declining numbers of Tcf1+ cells and result ultimately in reduced total numbers of pathogen-specific T-cells. Thus, we establish Tox as a critical factor for the development of T-cell dysfunction and establish a clear link between CD8 T-cell intrinsic suppression of effector function and protection against immune-pathology.
Overall design C57BL/6 mice engrafted with wt or Tox∆Ex5 2x10^3 P14 T-cells were infected with 2x10^6 PFU of LCMV clone-13. On day 8 post infection, splenic wt and Tox∆Ex5 P14 T-cells were sorted into Tim-3+ and Tim-3- T-cells and whole-genome DNA methylation analysis was performed as previously described (Ghoneim, et al. Cell 2017, PMID: 28648661). On day 8 and day 13 post infection, ATAC-seq was performed on splenic wt and Tox∆Ex5 P14 T-cells.
Contributor(s) Alfei F, Ghoneim HE, Fan Y, Youngblood B, Zehn D
Citation(s) 31207605
Submission date May 22, 2019
Last update date Jul 03, 2019
Contact name yiping fan
Phone 9015955716
Organization name st jude children's hospital
Street address 262 Danny Thomas Place
City memphis
State/province tn
ZIP/Postal code 38105
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM3791627 WT Tim3 -ve P14 T-cells_Day 8
GSM3791628 Tox∆Ex5 Tim3 -ve P14 T-cells_Day 8
GSM3791629 WT Tim3 +ve P14 T-cells_Day 8
This SubSeries is part of SuperSeries:
GSE131643 Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection
BioProject PRJNA544262
SRA SRP199205

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE131642_RAW.tar 548.2 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap