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| Status |
Public on Jun 23, 2020 |
| Title |
Early precursor T cells establish and propagate T cell exhaustion in chronic infection [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
TCF1+ precursors of exhausted T cells maintain T cell immunity during chronic infection and cancer and mediate the response to immune checkpoint inhibition; however, their developmental requirements are poorly understood. Here, we demonstrate that high antigen load promoted the differentiation of TCF1+ precursor T cells, which acquired hallmarks of T cell exhaustion such as impaired production of IFN? within the first days after infection. Transcriptional profiling revealed that exhaustion was established first in precursor T cells while early effector cells retained a polyfunctional profile. Early precursor T cells exposed to high amounts of antigen showed epigenetic imprinting of T cell receptor-dependent transcription factor binding, were dependent on BACH2 and restricted to the generation of T cells displaying features of exhaustion. Overall, we demonstrate that T cell exhaustion manifests first in TCF1+ precursor T cells and is propagated subsequently to the pool of antigen-specific T cells.
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| Overall design |
ATAC sequencing of ID3GFP+ and ID3GFP- P14 T cells obtained from early and late LCMV Armstrong and Docile infected mice.
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| Contributor(s) |
Utzschneider DT, Gabriel SS, Chisanga D, Gubser P, Shi W, Kallies A |
| Citation(s) |
32839610 |
| |
| Submission date |
Dec 24, 2019 |
| Last update date |
Aug 28, 2020 |
| Contact name |
Wei Shi |
| E-mail(s) |
wei.shi@onjcri.org.au
|
| Organization name |
Olivia Newton-John Cancer Research Institute
|
| Lab |
Bioinformatics and Cancer Genomics
|
| Street address |
Level 5, ONJ Cancer Centre, 145 Studley Rd
|
| City |
Heidelberg |
| State/province |
Victoria |
| ZIP/Postal code |
3084 |
| Country |
Australia |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE142687 |
Early precursor T cells establish and propagate T cell exhaustion in chronic infection |
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| Relations |
| BioProject |
PRJNA597483 |
| SRA |
SRP238701 |
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