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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 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\u2013CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mammalian target of rapamycin 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1402390","type":"journal-article","created":{"date-parts":[[2015,1,27]],"date-time":"2015-01-27T02:56:13Z","timestamp":1422327373000},"page":"2089-2098","source":"Crossref","is-referenced-by-count":43,"title":["Friends Not Foes: CTLA-4 Blockade and mTOR Inhibition Cooperate during CD8+ T Cell Priming To Promote Memory Formation and Metabolic Readiness"],"prefix":"10.1093","volume":"194","author":[{"given":"Virginia A","family":"Pedicord","sequence":"first","affiliation":[{"name":"Department of Immunology, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin R","family":"Cross","sequence":"additional","affiliation":[{"name":"Donald B. and Catherine C. 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