NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE246932 Query DataSets for GSE246932
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 (RNA-Seq)
Organism Mus musculus
Experiment type Expression 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 low input bulk RNAseq.
Web link https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691214/
 
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
E-mail(s) mprlic@fredhutch.org
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 (28)
GSM7881132 1_none
GSM7881133 2_TGFb
GSM7881134 3_none
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
Relations
BioProject PRJNA1035123

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
GSE246932_220809-P490-1_RawGeneCounts.csv.gz 1.5 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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