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

Interferon-producing killer dendritic cells (IKDCs) are a recently described subset of CD11c(lo)B220(+) 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 beta (IL-2R beta) chain but not those using the common gamma chain (gamma(c)) are necessary for their generation. By directly comparing Rag2(-/-)gamma(-/y)(c), Rag2(-/-)IL-2R beta(-/-), 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 Ncr1(gfp/+)gamma(-/y)(c) mice. Distinguishing features of IKDCs (CD11c(lo)B220(+)MHC-II(+)) were carefully examined on developing NK cells in the bone marrow and on peripheral NK cells. As B220 expression was heterogeneous, defining B220(lo) versus B220(hi) 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 CD11c(lo) B220(+) "IKDC-like" cells represent activated NK cells.