Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity

Abstract

Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses. We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-gamma, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro

“…Synergistic activity between IFN-y and TRAIL has been shown to down-regulate c-FLIP, sensitizing cells to apoptosis, making the two a potent combination (Stefanescu et al, 2008). TRAIL has also been found on IFN-y-producing killer dendritic cells (IKDCs), linking IFN-y TRAIL-induction to both the innate immune system and the adaptive immune system (Chan et al, 2006). Expression of TRAIL at the mRNA level has also been detected in peripheral lymphocytes after activation with monoclonal anti-CD3, an activator of T cells (Jeremias et al, 1998).…”

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

“…The main surface marker distinguishing such a population is B220, a high molecular weight (220 kDa) isoform of CD45 that was originally considered as a selective B-cell marker in mice. 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. [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.…”