期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 6, 页码 1593-1606出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20161760
关键词
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资金
- National Institutes of Health [1R01AI114442]
- ALSAC
Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell-mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T-EM), and longer-lived central memory (T-CM) and stem cell memory (T-SCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7- and IL-15-mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T-CM and T-SCM memory cells resulted in phenotypic conversion into T-EM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T-EM-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells.
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