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Cutting Edge: IFN- Signaling to Macrophages Is Required for Optimal V14i NK T/NK Cell Cross-Talk¹

Johnna D. Wesley^*, Scott H. Robbins^*, Stéphane Sidobre, Mitchell Kronenberg, Stephanie Terrizzi^* and Laurent Brossay^2,*

^* Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, RI 02912; and Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121

Activated NK T cells are known to rapidly stimulate NK cells and, subsequently, CD8⁺ T cells and B cells. In this report, we first demonstrate that the downstream effects induced by -galactosylceramide activated NK T cells on NK cells are mainly dependent on IFN-. We found that NK T cell activation of NK cells requires a functional IFN- signaling in macrophages and dendritic cells but not in B cells, NK cells, or NK T cells. NK T cell activation is dendritic cell-dependent whereas NK T cell activation of NK cells is indirect and in part mediated by macrophages. Interestingly, in this context, macrophage participation in the CD1d Ag presentation of -galactosylceramide to NK T cells is not necessary. These data indicate that NK T cell-dependent activation of macrophages is required for optimal NK T cell-induced stimulation of NK cells.

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