@Article{ecn.2010.0207,
AUTHOR = {Harmonie Perdreau, Erwan Mortier, Grégory Bouchaud, Véronique Solé, Yvan Boublik, Ariane Plet, Yannick Jacques},
TITLE = {Different dynamics of IL-15R activation following IL-15 <i>cis-</i> or <i>trans-</i>presentation},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {4},
PAGES = {297--307},
URL = {http://www.techscience.com/ECN/v21n4/65849},
ISSN = {1952-4005},
ABSTRACT = {Interleukin (IL)-15 is a cytokine critical for the homeostasis and the function of NK cells, NK-Tcells, and memory CD8+ T cells. IL-15 signals are delivered through the IL-15Rβ and the commonγ (γ<sub>c</sub>) receptorchains. The third receptor chain, IL-15Rα, confers specificity and high affinity for the cytokine. While IL-15 canactivate with high affinity the trimeric receptor expressed by a target cell (<i>cis-</i>presentation), IL-15Rα is alsoknown to <i>trans-</i>present IL-15 with high affinity to target cells expressing the IL-15Rβ/γ<sub>c</sub> complex. In order tocompare the IL-15 <i>cis-</i> and <i>trans-</i>presentation processes, and using a T cell line expressing both IL-15Rα/β/γ<sub>c</sub> andIL-15Rβ/γ<sub>c</sub>, we analyzed cell surface receptor chain down-modulation, cytokine internalization and signalingresponses induced either with IL-15 (<i>cis-</i>presentation) or with RLI, a protein resulting from fusion betweenIL-15 and an extended IL-15Rα sushi domain, that mimics <i>trans-</i>presentation. Whereas IL-15 bound with highaffinity to IL-15Rα/β/γ<sub>c</sub>, RLI bound with a similar high affinity to IL-15Rβ/γ<sub>c</sub>. The kinetics of cell surfaceIL-15R down-modulation were slower following RLI treatment than after IL-15 treatment, as were the kineticsof RLI internalization, which was slower than that of IL-15. IL-15 and RLI dose-dependently induced the activa-tion of similar signaling pathways. However, the kinetics and duration of these activations were markedly differ-ent, RLI-induced signaling, being slower, but more prolonged than that induced by IL-15, although the finalproliferative responses at 48 h were similar. These findings collectively indicate that IL-15 <i>cis-</i> and <i>trans-</i>presentation mechanisms lead to different dynamics of receptor activation and signal transduction, withcis-presentation inducing fast and transient responses, and <i>trans-</i>presentation inducing slower, more persistentones. They provide clues for a better understanding of how IL-15 action is controlled, and how it plays a keyrole in the coordination between innate and adaptative immunity.},
DOI = {10.1684/ecn.2010.0207}
}