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Author Notes:

To whom correspondence should be addressed. E-mail: rahmed@emory.edu.

Contributed by Rafi Ahmed, May 1, 2012 (sent for review December 18, 2011)

Author contributions: T.W. and R.A. designed research; T.W. and A.W. performed research; T.W., K.A., and C.W.D. contributed new reagents/analytic tools; T.W., L.Y., and R.A. analyzed data; and T.W., J.S.H., and R.A. wrote the paper.

Subject:

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

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 109, Number 25

Publisher:

, Pages 9965-9970

Type of Work:

Article | Post-print: After Peer Review

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.
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