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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 15, 2019 |
| Title |
Epigenetic signature of PD-1+ TCF1+ CD8 T cells thatact as resource cells during chronic viral infectionand respond to PD-1 blockade |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We have recently defined a novel population of PD-1+TCF1+virus-specific CD8 T cells that function as resource cells during chronic LCMV infection and provide the proliferative burst seen after PD-1 blockade. Such CD8 T cells have been found in other chronic infections and also in cancer in mice and humans. These CD8 T cells exhibit stem-like properties undergoing self-renewal and also giving rise to the terminally differentiated (exhausted) CD8 T cells. Here we compared the epigenetic signature of stem-like CD8 T cells with exhausted CD8 T cells. ATAC-seq analysis showed that stem-like CD8 T cells had a unique signature implicating activity of TCF (HMG family) and NF-κB (RHD family) members. In addition, transcription factor networks including Tcf7, Id3, and Bach2 were enriched in stem-like CD8 T cells. In contrast,exhausted CD8 T cells enriched accessible sites for ETS and Runx motifs in addition to a network encompassing Prdm1 and Il10. We also compared the epigenetic signatures of the two CD8 T-cellsubsets from chronically infected mice with effector and memory CD8 T cells generated after an acute LCMV infection. Both CD8T-cell subsets generated during chronic infection were strikingly different from CD8 T-cell subsets from acute infection. Interestingly, the stem-like CD8 T-cell subset from chronic infection, despite sharing key functional properties with memory CD8 T cells,had a very distinct epigenetic program. These results show that the chronic stem-like CD8 T-cell program represents a specific adaptation of the T-cell response to persistent antigenic stimulation.
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| Overall design |
RNA-seq analysis of CXCR5-Tim-3+ and CXCR5+Tim-3- CD8+ T-cell subsets, PD-1+CXCR5-Tim-3+CD8+ and PD-1+CXCR5+Tim-3-CD8+ cells (> 3x10e5 cells each) were sorted from pooled splenocytes of chronically LCMV infected mice (> day 40 p.i., n=14-15)
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| Contributor(s) |
Jadhav RR, Im SJ, Hu B, Hashimoto M, Li P, Lin J, Leonard WJ, Greenleaf WJ, Ahmed R, Goronzy JJ |
| Citation(s) |
31227606 |
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| Submission date |
Jun 03, 2019 |
| Last update date |
Jul 29, 2019 |
| Contact name |
Peng Li |
| E-mail(s) |
[email protected]
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| Organization name |
NIH
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| Department |
NHLBI
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| Lab |
LMI
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| Street address |
9000 Rockville Pike
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA545961 |
| SRA |
SRP200215 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE132110_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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