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Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):9965-70. doi: 10.1073/pnas.1207327109. Epub 2012 Jun 4.

Temporal expression of microRNA cluster miR-17-92 regulates effector and memory CD8+ T-cell differentiation.

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1
Emory Vaccine Center, and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Abstract

MicroRNAs are important regulators of various developmental and physiological processes. However, their roles in the CD8(+) T-cell response are not well understood. Using an acute viral infection model, we show that microRNAs of the miR-17-92 cluster are strongly induced after T-cell activation, down-regulated after clonal expansion, and further silenced during memory development. miR-17-92 promotes cell-cycle progression of effector CD8(+) T cells, and its expression is critical to the rapid expansion of these cells. However, excessive miR-17-92 expression enhances mammalian target of rapamycin (mTOR) signaling and strongly skews the differentiation toward short-lived terminal effector cells. Failure to down-regulate miR-17-92 leads to a gradual loss of memory cells and defective central memory cell development. Therefore, our results reveal a temporal expression pattern of miR-17-92 by antigen-specific CD8(+) T cells during viral infection, the precise control of which is critical to the effector expansion and memory differentiation of CD8(+) T cells.

PMID:
22665768
PMCID:
PMC3382487
DOI:
10.1073/pnas.1207327109
[Indexed for MEDLINE]
Free PMC Article
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