Immune Netw.  2007 Sep;7(3):133-140. 10.4110/in.2007.7.3.133.

Inflammatory Mediators Modulate NK Cell-stimulating Activity of Dendritic Cells by Inducing Development of Polarized Effector Function

• Kim KD
• Choi SC
• Lee ES
• Kim A
• Lim JS

• KMID: 1513199
• DOI: http://doi.org/10.4110/in.2007.7.3.133

Abstract

BACKGROUND: It is well established that cross talk between natural killer (NK) cells and myeloid dendritic cells (DC) leads to NK cell activation and DC maturation. In the present study, we investigated whether type 1-polarized DC (DC1) matured in the presence of IFN-gamma and type 2-polarized DC (DC2) matured in the presence of PGE2 can differentially activate NK cells.
METHODS
In order to generate DC, plastic adherent monocytes were cultured in RPMI 1640 containing GM-CSF and IL-4. At day 6, maturation was induced by culturing the cells for 2 days with cytokines or PGE2 in the presence or absence of LPS. Each population of DC was cocultured with NK cells for 24 h. The antigen expression on DC was analyzed by flow cytometry and cytokine production in culture supernatant was measured by ELISA or a bioassay for TNF-alpha determination. NK cell-mediated lysis was determined using a standard 4 h chromium release assay.
RESULTS
DC2, unlike DC1, had weak, if any, ability to induce NK cell activation as measured by IFN-gamma production and cytolytic activity. DC2 were weakly stimulated by activated NK cells compared to DC1. In addition, IFN-gamma-primed mature DC appeared to be most resistant to active NK cell-mediated lysis even at a high NK cell/DC ratio. On the other hand, PGE2-primed DC were less resistant to feedback regulation by NK cells than IFN-gamma-primed mature DC. Finally, we showed that the differential effect of two types of DC population on NK cell activity is not due to differences in their ability to form conjugates with NK cells.
CONCLUSION
These results suggest that different combinations of inflammatory mediators differentially affect the effector function of DC and, as a result, the function of NK cells, eventually leading to distinct levels of activation in adaptive immunity.

Keyword

DC; NK cells; cytokine production; PGE2; NK cell-mediated killing

MeSH Terms

Adaptive Immunity
Biological Assay
Chromium
Cytokines
Dendritic Cells*
Dinoprostone
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor
Hand
Interleukin-4
Killer Cells, Natural
Monocytes
Plastics
Tumor Necrosis Factor-alpha
Chromium
Cytokines
Dinoprostone
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Plastics
Tumor Necrosis Factor-alpha