Trans-presentation of IL-15 dictates IFN-producing killer dendritic cells effector functions

Ullrich E, Bonmort M, Mignot G, Jacobs B, Bosisio D, Sozzani S, Jalil A, Louache F, Bulanova E, Geissman F, Ryffel B, Chaput N, Bulfone-Paus S, Zitvogel L.
J Immunol. 2008 Jun 15;180(12):7887-97.

IFN-producing killer dendritic cells (IKDC) were initially described as B220(+)CD11c(+)CD3(-)NK1.1(+) tumor-infiltrating cells that mediated part of the antitumor effects of the combination therapy with imatinib mesylate and IL-2. In this study, we show their functional dependency on IL-15 during homeostasis and inflammatory processes. Trans-presentation of IL-15 by IL-15Ralpha allows dramatic expansion of IKDC in vitro and in vivo, licenses IKDC for TRAIL-dependent killing and endows IKDC with immunizing potential, all three biological attributes not shared by B220(-)NK cells. However, IL-15 down-regulates the capacity of IKDC to induce MHC class I- or II-restricted T cell activation in vitro. Trans-presentation of IL-15 by IL-15Ralpha allows IKDC to respond to TLR3 and TLR4 ligands for the production of CCL2, a chemokine that is critical for IKDC trafficking into tumor beds (as described recently). We conclude that IKDC represent a unique subset of innate effectors functionally distinguishable from conventional NK cells in their ability to promptly respond to IL-15-driven inflammatory processes.

URL: http://www.jimmunol.org/cgi/content/full/180/12/7887

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/18523252

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