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Cross-Talk between Activated Human NK Cells and CD4⁺ T Cells via OX40-OX40 Ligand Interactions¹

Alessandra Zingoni^*,, Thierry Sornasse^2,, Benjamin G. Cocks, Yuetsu Tanaka, Angela Santoni and Lewis L. Lanier^3,*

^* Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143; Department of Experimental Medicine and Pathology, University of Rome "La Sapienza", Rome, Italy; Incyte Corporation, Palo Alto, CA 94304; and Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

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- produced by autologous CD4⁺ T cells and this process is dependent upon expression of OX40 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.

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