The Journal of Experimental Medicine
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Published online October 8, 2007
doi:10.1084/jem.20071451
The Journal of Experimental Medicine, Vol. 204, No. 11, 2569-2578
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Vosshenrich et al.
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BRIEF DEFINITIVE REPORT

 CD11cloB220+ interferon-producing killer dendritic cells are activated natural killer cells

Christian A.J. Vosshenrich1,2, Sarah Lesjean-Pottier1,2, Milena Hasan1,2, Odile Richard-Le Goff1,2, Erwan Corcuff1,2, Ofer Mandelboim3, and James P. Di Santo1,2

1 Unité des Cytokines et Développement Lymphoide, Institut Pasteur, 75015 Paris, France
2 Institut National de la Santé et de la Recherche Médicale U668, 75015 Paris, France
3 The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel

CORRESPONDENCE James P. Di Santo: disanto{at}pasteur.fr

Interferon-producing killer dendritic cells (IKDCs) are a recently described subset of CD11cloB220+ cells that share phenotypic and functional properties of DCs and natural killer (NK) cells (Chan, C.W., E. Crafton, H.N. Fan, J. Flook, K. Yoshimura, M. Skarica, D. Brockstedt, T.W. Dubensky, M.F. Stins, L.L. Lanier, et al. 2006. Nat. Med. 12:207–213; Taieb, J., N. Chaput, C. Menard, L. Apetoh, E. Ullrich, M. Bonmort, M. Pequignot, N. Casares, M. Terme, C. Flament, et al. 2006. Nat. Med. 12:214–219). IKDC development appears unusual in that cytokines using the interleukin (IL)-2 receptor ß (IL-2Rß) chain but not those using the common {gamma} chain ({gamma}c) are necessary for their generation. By directly comparing Rag2–/–{gamma}c–/y, Rag2–/–IL-2Rß–/–, Rag2–/–IL-15–/–, and Rag2–/–IL-2–/– mice, we demonstrate that IKDC development parallels NK cell development in its strict IL-15 dependence. Moreover, IKDCs uniformly express NK-specific Ncr-1 transcripts (encoding NKp46), whereas NKp46+ cells are absent in Ncr1gfp/+{gamma}c–/y mice. Distinguishing features of IKDCs (CD11cloB220+MHC-II+) were carefully examined on developing NK cells in the bone marrow and on peripheral NK cells. As B220 expression was heterogeneous, defining B220lo versus B220hi NK1.1+ NK cells could be considered as arbitrary, and few phenotypic differences were noted between NK1.1+ NK cells bearing different levels of B220. CD11c expression did not correlate with B220 or major histocompatibility complex (MHC) class II (MHC-II) expression, and most MHC-II+ NK1.1+ cells did not express B220 and were thus not IKDCs. Finally, CD11c, MHC-II, and B220 levels were up-regulated on NK1.1+ cells upon activation in vitro or in vivo in a proliferation-dependent fashion. Our data suggest that the majority of CD11cloB220+ "IKDC-like" cells represent activated NK cells.


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