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E-GEOD-63022 - Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming

Status
Released on 31 January 2015, last updated on 8 February 2015
Organism
Mus musculus
Samples (18)
Array (1)
Protocols (7)
Description
T cells receive numerous positive and negative signals during primary antigen encounter that control their proliferation and function, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mTOR inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8+ T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8+ T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8+ T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mTOR inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation and an optimal metabolic program for CD8+ T cell memory. Total RNA was isolated from FACS-sorted, antigen-specific CD8+T cells from different treatment conditions at 5 or 35 days after primary T cell activation
Experiment type
transcription profiling by array 
Contacts
Martin L Miller <martin.miller@cruk.cam.ac.uk>, James P Allison, Justin R Cross, Virginia A Pedicord, Welby Montalvo-Ortiz
Citation
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-63022.idf.txt
Sample and data relationshipE-GEOD-63022.sdrf.txt
Processed data (1)E-GEOD-63022.processed.1.zip
Additional data (1)E-GEOD-63022.additional.1.zip
Array designA-MEXP-1175.adf.txt
Links