Logo image
Back
In vitro enhancing oxidative phosphorylation by rapamycin in proliferative CD8+ T cells during antigenic priming augments the generation of long-lived memory T cells in vivo (101.11)
Journal article   Peer reviewed

In vitro enhancing oxidative phosphorylation by rapamycin in proliferative CD8+ T cells during antigenic priming augments the generation of long-lived memory T cells in vivo (101.11)

Shan He, Koji Kato, Jiu Jiang, Daniel Wahl, Shin Mineishi, Shuaiying Cui, Gary Glick, Donna Murasko and Yi Zhang
The Journal of immunology (1950), v 184(1_Supplement), pp 101-101.11
01 Apr 2010
DOI: https://doi.org/10.4049/jimmunol.184.Supp.101.11

Abstract

Abstract Oxidative phosphorylation is critical to the transition of effectors to memory T cells. However, whether increasing oxidative phosphorylation in proliferative CD8+ T cells during antigenic priming can augment memory T cell generation remains unknown. Using T cell receptor transgenic CD8+ T cells, we found that rapamycin significantly increased the oxidative phosphorylation in antigen-primed naïve CD8+ T cells in vitro without inhibiting their activation and proliferation. Augmented oxidative phosphorylation endowed the rapamycin-treated T cells great ability to survive after IL-2 withdrawal, whereas all the untreated control cells rapidly diminished. Rapamycin-treated CD8+ T cells expressed high levels of CD62L and CD127 but low levels of KLRG-1, PD-1 and IFN-γ. When adoptively transferred in vivo, CD8+ T cells derived from rapamycin-treated cultures generated 5-fold more memory T cells over a period of 6 months than control cells. These long-lived memory T cells had potent ability to produce IFN-γ and proliferate when reexposed to the specific antigen both in vivo and in vitro. These data indicate that augmentation of oxidative phosphorylation in T cells by rapamycin in vitro during antigenic priming dramatically increases both the number and quality of memory precursors, thereby enhancing the generation of long-lived memory T cells. Our findings may have significant implications in optimizing T cell properties to improve the efficacy of adoptive immunotherapy.

Metrics

7 Record Views

Details

Logo image