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

Abstract

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 β (IL-2Rβ) chain but not those using the common γ chain (γc) are necessary for their generation. By directly comparing Rag2−/−γc −/y, Rag2−/−IL-2Rβ−/−, 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/+γc −/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.

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells

“…6,7 However, several groups have recently questioned the existence of this cell subset as a separate lineage from NK cells, with the putative antigen presentation function of IKDC at the core of the controversy. [8][9][10] For some of these authors, IKDCs may represent an activated status of conventional NK cells. 8 IL-15 11,12 is an absolutely essential cytokine for the differentiation and maintenance of memory CD8 + T, NKT and NK cells.…”

NK cells from tuberculous pleurisy express high ICAM‐1 levels and exert stimulatory effect on local T cells

“…These unconventional capabilities include [16,17,18] and direct pathogen recognition [19,20]. In this regard, a novel innate immune cell population called Interferon-producing killer dendritic cells has been recently described in mice [21,22].…”

“…These unconventional capabilities include [16,17,18] and direct pathogen recognition [19,20]. In this regard, a novel innate immune cell population called Interferon-producing killer dendritic cells has been recently described in mice [21,22].ICAM-1/CD54 is the major ligand of costimulatory a L b 2 integrin (CD11a/CD18), commonly known as lymphocyte function-associated antigen (LFA-1) [23,24]. The surface enhancement of ICAM-1 on endothelial, APC and B cells have pleiotropic effects in LFA-1-mediated T lymphocyte responses including T-cell homing [25], formation and stabilization of immunosynapse [26,27], T-cell memory differentiation [28], and Th1 polarization [29,30], among others.…”

Proliferating NK cells in response to IL-15 do not upregulate surface B220 in vivo

“…1,2 Other authors contend that these cells represent activated NK cells, as classical NK cells (cNK) (DX5 + CD3 À NK1.1 + B220 À ) acquire B220 on activation. [3][4][5] Recently, we reported that productive in vivo transfer of the IL-15 gene into the liver by hydrodynamic injection results in the proliferation and activation of both cNK cells and IKDC. 6 Furthermore, in the context of in vivo gene transfer of IL-15 into hepatocytes, 6 we made other observations centered on both the function and ontogeny of IKDC, which are relevant to this controversy.…”

“…6 Furthermore, in the context of in vivo gene transfer of IL-15 into hepatocytes, 6 we made other observations centered on both the function and ontogeny of IKDC, which are relevant to this controversy. [1][2][3][4][5]7 DX5 + cells from the spleen of B6.SJL-Ptprc a Pep3 b / BoyJ mice (CD45.1 mice) were analyzed by fluorescence-activated cell sorting (FACS) analysis (to 98-99% purity) into DX5 + CD3 À NK1.1 + B220 À (cNK) and DX5 + CD3 À NK1.1 + B220 + (IKDC) fractions. Both populations once labeled by CFSE (carboxyfluorescein diacetate succinimidyl ester) were adoptively transferred into congenic C57BL/6J (CD45.2) mice, which had been hydrodynamically injected with the IL-15-encoding (pVKL/IL15IRESNeo) or control (pIRESNeo) plasmid 8 h before adoptive transfer, as detailed in Arina et al 6 Immunostaining of the CD45.1/CD45.2 polymorphism permitted unequivocal gating of the adoptively transferred cells.…”