Transcriptomics

Dataset Information

4

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


ABSTRACT: 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

ORGANISM(S): Mus musculus  

SUBMITTER: James P Allison   Welby Montalvo-Ortiz  Martin L Miller  Virginia A Pedicord  Justin R Cross 

PROVIDER: E-GEOD-63022 | ArrayExpress | 2015-01-31

SECONDARY ACCESSION(S): GSE63022PRJNA266447

REPOSITORIES: GEO, ArrayExpress

altmetric image

Publications

Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness.

Pedicord Virginia A VA   Cross Justin R JR   Montalvo-Ortiz Welby W   Miller Martin L ML   Allison James P JP  

Journal of immunology (Baltimore, Md. : 1950) 20150126 5


During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, and differentiation, 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 mammalian target of rapamycin inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8(+) T cells  ...[more]

Similar Datasets

2014-09-20 | E-GEOD-61591 | ArrayExpress
2015-06-16 | E-GEOD-67593 | ArrayExpress
| GSE100808 | GEO
| GSE100807 | GEO
2016-02-16 | E-GEOD-77924 | ArrayExpress
2012-09-05 | E-GEOD-37563 | ArrayExpress
2016-02-10 | E-GEOD-77714 | ArrayExpress
2010-07-09 | E-GEOD-21360 | ArrayExpress
2014-10-07 | E-GEOD-62089 | ArrayExpress
2009-06-24 | E-GEOD-15750 | ArrayExpress