Vγ2Vδ2 T-cell co-stimulation increases natural killer cell killing of monocyte-derived dendritic cells

Interactions between natural killer (NK) cells and dendritic cells (DC) affect maturation and function of both cell populations, including NK cell killing of DC (editing), which is important for controlling the quality of immune responses. We also know that antigen-stimulated V gamma 2V delta 2 T cells co-stimulate NK cells via 4-1BB to enhance the killing of tumour cell lines but we do not know what regulates 4-1BB expression or whether other NK effector functions including DC killing, might also be influenced by NK-gamma delta T-cell cross-talk. Here we show that antigen-stimulated gamma delta T cells co-stimulate NK cells through inducible T-cell co-stimulator (ICOS)-ICOS ligand (ICOSL) and this signal increases NK cell killing of autologous DC. Effects of NK-gamma delta T-cell co-culture, which could be reproduced with soluble ICOS-Fc fusion protein, included increased CD69 and 4-1BB expression, interferon-c, tumour necrosis factor-alpha, macrophage inflammatory protein-1 beta, I-309, RANTES and sFas ligand production, as well as elevated mRNA levels for co-stimulatory receptors OX40 (TNFRSF4) and GITR (TNFRSF18). Hence, ICOS-ICOSL co-stimulation of NK by V gamma 2V delta 2 T cells had broad effects on NK phenotype and effector functions. The NK-gamma delta T-cell cross-talk links innate and antigen-specific lymphocyte responses in the control of cytotoxic effector function and DC killing.