Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness Journal Article
| Authors: | Pedicord, V. A.; Cross, J. R.; Montalvo Ortiz, W.; Miller, M. L.; Allison, J. P. |
| Article Title: | Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness |
| Abstract: | 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 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 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. Copyright © 2015 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; controlled study; nonhuman; cd8+ t lymphocyte; lymphocyte proliferation; animal cell; mouse; cytotoxic t lymphocyte antigen 4 antibody; enzyme inhibition; animal experiment; animal model; in vivo study; lymphocyte differentiation; nucleotide sequence; mammalian target of rapamycin; tumor cell; cytotoxic t lymphocyte antigen 4; rapamycin; mitochondrion; lymphocyte function; biogenesis; immunization; memory t lymphocyte; cell priming; cell respiration; cellular parameters; priority journal; article |
| Journal Title: | Journal of Immunology |
| Volume: | 194 |
| Issue: | 5 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2015-03-01 |
| Start Page: | 2089 |
| End Page: | 2098 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1402390 |
| PROVIDER: | scopus |
| PUBMED: | 25624453 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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