Cross-talk between activated human NK cells and CD4+ T cells via OX40-OX40 ligand interactions

It is important to understand which molecules are relevant for linking innate and adaptive immune cells. In this study, we show that OX40 ligand is selectively induced on IL-2, IL-12, or IL-15-activated human NK cells following stimulation through NKG2D, the low affinity receptor for IgG (CD16) or killer cell Ig-like receptor 2DS2. CD16-activated NK cells costimulate TCR-induced proliferation, and IFN-γ produced by autologous CD4⁺ T cells and this process is dependent upon expression of OX46 ligand and B7 by the activated NK cells. These findings suggest a novel and unexpected link between the natural and specific immune responses, providing direct evidence for cross-talk between human CD4⁺ T cells and NK receptor-activated NK cells.