Freshly isolated peripheral blood NK granular lymphocytes (GL) and NK cell lines derived from 13 different NK-LDGL patients were analyzed in coculture experiments to evaluate their ability to interact with monocyte-derived DCs (Mo-DC).
As compared to NK cells isolated from healthy donors, NK-GLs displayed, in most cases, a reduced capability of promoting Mo-DC maturation and of killing iDC. These findings could be explained, at least in part, by the low expression levels of NKp30: an activating receptor involved in the molecular interactions occurring between NK cells and DC. We also show that, in the presence of DC-derived cytokines such as interleukin-12, in both patients and healthy individuals, DNAM-1 can cooperate with NKp30 to induce NK cells to kill DC, release tumor necrosis factor – α, and promote DC maturation. This contribution, however, is not sufficient to compensate for the defect in patients' NK cells.
Besides expanding knowledge of the molecular basis of the NK/DC cross-talk, our study demonstrates that NK cells from NK-LDGL patients are impaired in their ability to interact with Mo-DC. The possible relationship between such abnormal NK cell/DC interactions and chronic NK cell proliferation are discussed.