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Series GSE246930 Query DataSets for GSE246930
Status Public on Nov 05, 2023
Title TGF-β broadly modifies rather than specifically suppresses reactivated memory CD8 T cells in a dose-dependent manner (ATAC-Seq)
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Transforming growth factor β (TGF-β) directly acts on naïve, effector and memory T cells to control cell fate decisions, which was shown using genetic abrogation of TGF-β signaling. TGF-β availability is altered by infections and cancer, however the dose-dependent effects of TGF-β on memory CD8 T cell (Tmem) reactivation are still poorly defined. We examined how activation and TGF-β signals interact to shape the functional outcome of Tmem reactivation. We found that TGF-β could suppress cytotoxicity in a manner that was inversely proportional to the strength of the activating TCR or pro-inflammatory signals. In contrast, even high doses of TGF-β had a comparatively modest effect on IFN-γ expression in the context of weak and strong reactivation signals. Since CD8 Tmem may not always receive TGF-β signals concurrently with reactivation, we also explored whether the temporal order of reactivation versus TGF-β signals is of importance. We found that exposure to TGF-β prior to as well as after an activation event were both sufficient to reduce cytotoxic effector function. Concurrent ATAC-seq and RNA-seq analysis revealed that TGF-β altered ~10% of the regulatory elements induced by reactivation and also elicited transcriptional changes indicative of broadly modulated functional properties. We confirmed some changes on the protein level and found that TGF-β-induced expression of CCR8 was inversely proportional to the strength of the reactivating TCR signal. Together, our data suggest that TGF-β is not simply suppressing CD8 Tmem, but modifies functional and chemotactic properties in context of their reactivation signals and in a dose-dependent manner.
Overall design OT-1 memory mice were harvested for secondary lymphoid organs (lymph nodes and spleen). A T cell isolation was performed to isolate T cells. T cells were plated for 2 hours with or without TGFb and for 24 hours with SIINFEKL and TGFb or SIINFEKL alone. OT-1 cells (CD45.1 and CD8+) were FACS sorted for downstream analysis by bulk RNAseq and bulk ATACseq.
Web link
Contributor(s) Taber A, Konecny AJ, Oda S, Scott-Browne J, Prlic M
Citation(s) 37988468
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 AI123323 Inflammation-driven T Cell Responses and their Dichotomous Effect on Host Immunity FRED HUTCHINSON CANCER CENTER Martin Prlic
R01 AI151021 Transcriptional Control of T Cell Function NATIONAL JEWISH HEALTH James Scott-Browne
Submission date Nov 02, 2023
Last update date Feb 05, 2024
Contact name Martin Prlic
Phone 2066672216
Organization name Fred Hutchinson Cancer Center
Lab Prlic
Street address 1100 Fairview Ave, Mail stop E5-110
City Seattle
State/province WA
ZIP/Postal code 98102
Country USA
Platforms (1)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (12)
GSM7881000 1_3_5_none
GSM7881001 2_4_6_TGFb
GSM7881002 7_9_11_SIINFEKL
This SubSeries is part of SuperSeries:
GSE246933 TGF-β broadly modifies rather than specifically suppresses reactivated memory CD8 T cells in a dose-dependent manner
BioProject PRJNA1035122

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Supplementary file Size Download File type/resource
GSE246930_results.log2cpm.kbMean.tsv.gz 3.3 Mb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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