Journal
IMMUNOLOGY
Volume 120, Issue 1, Pages 73-82Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1365-2567.2006.02479.x
Keywords
NK receptor; regulatory T cell; HLA-E; liver; HCV
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Natural killer (NK) cells have the ability to control dendritic cell (DC)-mediated T cell responses. However, the precise mechanisms by which NK receptor-mediated regulation of NK cells determines the magnitude and direction of DC-mediated T cell responses remain unclear. In the present study, we applied an in vitro co-culture system to examine the impact of NK cells cultured with hepatic cells on DC induction of regulatory T cells. We found that interaction of NK cells and non-transformed hepatocytes (which express HLA-E) via the NKG2A inhibitory receptor resulted in priming of DCs to induce CD4(+) CD25(+) T cells with regulatory properties. NKG2A triggering led to characteristic changes of the cytokine milieu of co-cultured cells; an increase in the transforming growth factor (TGF)-beta involved in the generation of this specific type of DC, and a decrease in the tumour necrosis factor-alpha capable of antagonizing the effect of TGF-beta. The regulatory cells induced by NK cell-primed DCs exert their suppressive actions through a negative costimulator programmed death-1 (PD-1) mediated pathway, which differs from freshly isolated CD4(+) CD25(+) T cells. These findings provide new insight into the role of NK receptor signals in the DC-mediated induction of regulatory T cells.
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