Abstract |
Dendritic cells (DCs) augment effector functions of NK cells, but the underlying mechanisms are not fully understood. Here we show in an in vitro coculture system that human monocyte-derived DCs enhance IFN-gamma production, CD69 expression, and K562 cytolytic ability of NK cells when DCs are prestimulated with various maturation stimuli such as IFN-alpha or LPS. Of interest is the finding that NK cell activation mediated by LPS-stimulated DCs was dependent on IL-12 produced in DC/NK coculture, but that IFN-alpha-stimulated DC-mediated activation was not. Alternatively, MHC class I-related chain A and B ( MICA/B), ligands for NKG2D activating receptor, were found to be induced on DCs upon IFN-alpha stimulation and to be responsible for the NK activation because mAb-mediated masking of MICA/B as well as inhibition of direct cell-to-cell contact using transwell insert completely abolished DC-dependent NK cell activation by IFN-alpha. Finally, DCs recovered from chronic hepatitis C virus-infected patients showed defects in the induction of MICA/B and impaired ability to activate NK cells in response to IFN-alpha stimulation. These findings suggested that MICA/B induction on DCs may be one of the mechanisms by which IFN-alpha activates NK cells; this impairment might affect IFN-alpha responsiveness in hepatitis C virus infection.
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Authors | Masahisa Jinushi, Tetsuo Takehara, Tatsuya Kanto, Tomohide Tatsumi, Veronika Groh, Thomas Spies, Takuya Miyagi, Takahiro Suzuki, Yutaka Sasaki, Norio Hayashi |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 170
Issue 3
Pg. 1249-56
(Feb 01 2003)
ISSN: 0022-1767 [Print] United States |
PMID | 12538683
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, CD
- Antigens, Differentiation, T-Lymphocyte
- CD69 antigen
- Histocompatibility Antigens Class I
- Interferon-alpha
- Lectins, C-Type
- Lipopolysaccharides
- MHC class I-related chain A
- MICB antigen
- Protein Subunits
- Interleukin-12
- Interferon-gamma
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Topics |
- Antigens, CD
(biosynthesis)
- Antigens, Differentiation, T-Lymphocyte
(biosynthesis)
- Cell Communication
(immunology)
- Cell Differentiation
(immunology)
- Cells, Cultured
- Coculture Techniques
- Cytotoxicity, Immunologic
- Dendritic Cells
(cytology, immunology, metabolism, pathology)
- Hepacivirus
(immunology)
- Hepatitis C, Chronic
(immunology, pathology)
- Histocompatibility Antigens Class I
(biosynthesis, physiology)
- Humans
- Interferon-alpha
(pharmacology)
- Interferon-gamma
(biosynthesis)
- Interleukin-12
(physiology)
- K562 Cells
- Killer Cells, Natural
(immunology)
- Lectins, C-Type
- Lipopolysaccharides
(pharmacology)
- Lymphocyte Activation
- Protein Subunits
(biosynthesis, physiology)
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