Details

Autor(en) / Beteiligte

• Zhang, Nu
• Bevan, Michael J.

Titel

Dicer controls CD8⁺ T-cell activation, migration, and survival

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2010-12, Vol.107 (50), p.21629-21634

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The RNaseIII enzyme Dicer is required for mature microRNA production. Although extensive investigation has been carried out to determine the role of Dicer/miRNAs in the immune system, their function in mature CD8⁺ T cells has not been examined. We deleted Dicer in mature polyclonal and TCR transgenic CD8⁺ T cells using either tat-cre or the distal lck promoter, which drives cre expression after the stage of positive selection. Following antigenic challenge by a pathogen infection in vivo, Dicer-deleted CD8⁺ T cells failed to accumulate at the usual peak of the response. Surprisingly however, we found that deletion of Dicer in mature CD8⁺ T cells allowed them to respond more rapidly than control cells to TCR stimuli in vitro. In response to anti-CD3 plus anti-CD28 stimulation, Dicer-deleted T cells up-regulated CD69 faster and entered the first mitosis earlier than control T cells. In addition, activated Dicer -/- cells failed to rapidly down-regulate CD69 when removed from the TCR stimulus. As a probable consequence of this sustained CD69 expression, Dicer -/- T cells showed defective migration out of the central lymphoid organs in vivo. We identify miR-130/301, which are dramatically up-regulated following T-cell activation, as able to down-regulate CD69 expression via binding to a conserved site in the 3'UTR of CD69 mRNA. Thus, cellular functions dependent on Dicer expression are not required for the early steps in CD8⁺ T-cell activation, but are essential for their survival and accumulation.