Cytolysis of human dendritic cells by autologous lymphokine-activated killer cells: participation of both T cells and NK cells in the killing

Dendritic cells (DC) play a key role in the initiation of immune response b y stimulating the naive T cells. The fate of DC after the initiation of imm une response is not clearly understood. Although there are fe tv reports im plicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. in this s tudy, we observed that DC, generated from monocytes, in vitro in the presen ce of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4 ), and tumor necrosis factor alpha were susceptible to cytolysis by lymphok ine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 a nd suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8(+)/CD57(-) fraction (T-LAK), but not the CD8(-)/CD57(+) fraction (NK-LAK) was cytotoxic to autologous DC. However, w hen unseparated peripheral blood mononuclear cells T were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity agains t autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 signif icantly inhibited the cytolysis, indicating that the killing involves the e ngagement of CD54 with its ligands.