期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：23
页码：8565-8570
DOI：10.1073/pnas.1405514111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Interleukin (IL)-15 and its specific receptor chain, IL-15R, support the development of various effector cells, including NK and CD8 T cells via a mechanism called trans-presentation. Whereas the dynamic of trans-presentation has been shown to involve the recycling of IL-15R by presenting cells, the way responding cells integrate, or take advantage of this process has not been evaluated yet. To address this question, we set up a trans-presentation model using a membrane-bound IL-15.IL-15R fusion protein, and found that IL-15 is detectable within responding cells following IL-15 trans-presentation. The role of the proteolytic cleavage of IL-15R in this process was investigated by generating an uncleavable form of IL-15R. We showed that IL-15 entry into responding cells necessitates the cleavage of IL-15.IL-15R complex from the surface of IL-15 presenting cells, and observed that IL-15R cleavage is associated with a decrease of the duration of Stat5 signaling. Once separated from presenting cells, responding cells are able to recycle IL-15.IL-15R complexes via intracellular compartments, for residual proliferation in a time-limited manner. These studies define an unprecedented cytokine pathway in which the IL-15.IL-15R complex cleaved from presenting cells allows responding cells to internalize, store and use IL-15.IL-15R complex for their own proliferation and survival.
