CD 4 + NKG 2 D + T cells induce NKG 2 D down‐regulation in natural killer cells in CD 86‐ RAE ‐1 ε transgenic mice

Summary The binding of NKG 2 D to its ligands strengthens the cross‐talk between natural killer ( NK ) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript‐1 ε ( RAE ‐1 ε ), one of the ligands of NK G2 D , was persistently expressed on antigen‐presenting cells in a transgenic mouse model (p CD 86‐ RAE ‐1 ε ). By contrast, NKG 2 D expression on NK cells, NKG 2 D ‐dependent cytotoxicity and tumour rejection, and dextran sodium sulphate‐induced colitis were all down‐regulated in this mouse model. The down‐regulation of NKG 2 D on NK cells was reversed by stimulation with poly ( I : C ). The ectopic expression of RAE ‐1 ε on dendritic cells maintained NKG 2 D expression levels and stimulated the activity of NK cells ex vivo , but the higher frequency of CD 4 +   NKG 2 D + T cells in transgenic mice led to the down‐regulation of NKG 2 D on NK cells in vivo . Hence, high levels of RAE ‐1 ε expression on antigen‐presenting cells would be expected to induce the down‐regulation of NK cell activation by a regulatory T ‐cell subset.