Interferon-producing killer dendritic cells (IKDCs) have been described as possessing the lytic potential of NK cells and the antigen-presenting capacity of dendritic cells (DCs). In this study, we examine the lytic function and antigen-presenting capacity of mouse spleen IKDCs, including those found in DC preparations. IKDCs efficiently killed NK cell targets, without requiring additional activation stimuli. However, in our hands, when exposed to protein antigen or to MHC class II peptide, IKDCs induced little or no T cell proliferation relative to conventional DCs or plasmacytoid DCs, either before or after activation with CpG, or in several disease models. Certain developmental features indicated that IKDCs resembled NK cells more than DCs. IKDCs, like NK cells, did not express the transcription factor PU.1 and were absent from recombinase activating gene-2–null, common γ-chain–null (Rag2−/−Il2rg−/−) mice. When cultured with IL-15 and -18, IKDCs proliferated extensively, like NK cells. Under these conditions, a proportion of expanded IKDCs and NK cells expressed high levels of surface MHC class II. However, even such MHC class II+ IKDCs and NK cells induced poor T cell proliferative responses compared with DCs. Thus, IKDCs resemble NK cells functionally, and neither cell type could be induced to be effective antigen-presenting cells.
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29 October 2007
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October 08 2007
Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells
Irina Caminschi,
Irina Caminschi
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Fatma Ahmet,
Fatma Ahmet
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Klaus Heger,
Klaus Heger
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Jason Brady,
Jason Brady
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Stephen L. Nutt,
Stephen L. Nutt
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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David Vremec,
David Vremec
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Suzanne Pietersz,
Suzanne Pietersz
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Mireille H. Lahoud,
Mireille H. Lahoud
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Louis Schofield,
Louis Schofield
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Diana S. Hansen,
Diana S. Hansen
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Meredith O'Keeffe,
Meredith O'Keeffe
2Bavarian Nordic GmbH, Munich D-82152, Germany
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Mark J. Smyth,
Mark J. Smyth
3Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, 3002, Victoria, Australia
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Sammy Bedoui,
Sammy Bedoui
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Gayle M. Davey,
Gayle M. Davey
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Jose A. Villadangos,
Jose A. Villadangos
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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William R. Heath,
William R. Heath
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Ken Shortman
Ken Shortman
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
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Irina Caminschi
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Fatma Ahmet
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Klaus Heger
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Jason Brady
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Stephen L. Nutt
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
David Vremec
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Suzanne Pietersz
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Mireille H. Lahoud
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Louis Schofield
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Diana S. Hansen
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Meredith O'Keeffe
2Bavarian Nordic GmbH, Munich D-82152, Germany
Mark J. Smyth
3Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, 3002, Victoria, Australia
Sammy Bedoui
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Gayle M. Davey
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Jose A. Villadangos
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
William R. Heath
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
Ken Shortman
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, 3050, Australia
CORRESPONDENCE Irina Caminschi: [email protected]
Abbreviations used: cDC, conventional DC; CHO, chinese hamster ovary; IKDC, IFN-producing killer DC; pDC, plasmacytoid DC; PI, propidium iodide; SA, streptavidin.
Received:
July 02 2007
Accepted:
September 24 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (11): 2579–2590.
Article history
Received:
July 02 2007
Accepted:
September 24 2007
Citation
Irina Caminschi, Fatma Ahmet, Klaus Heger, Jason Brady, Stephen L. Nutt, David Vremec, Suzanne Pietersz, Mireille H. Lahoud, Louis Schofield, Diana S. Hansen, Meredith O'Keeffe, Mark J. Smyth, Sammy Bedoui, Gayle M. Davey, Jose A. Villadangos, William R. Heath, Ken Shortman; Putative IKDCs are functionally and developmentally similar to natural killer cells, but not to dendritic cells . J Exp Med 29 October 2007; 204 (11): 2579–2590. doi: https://doi.org/10.1084/jem.20071351
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