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IL-18 Bridges Innate and Adaptive Immunity through IFN- and the CD134 Pathway¹

Joseph R. Maxwell^2,*, Rajwardhan Yadav^*, Robert J. Rossi^*, Carl E. Ruby, Andrew D. Weinberg, Hector L. Aguila^* and Anthony T. Vella^3,*

^* Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and Providence Medical Center, Portland, OR 97213

IL-18 induces inflammation resulting in either enhanced protection from pathogens or exacerbation of autoimmunity, and T cells are profoundly activated during these responses. How IL-18 influences T cell activation is unknown, but this study in mice shows that IL-18 boosted Ag-specific T cell clonal expansion of effector T cells and induced a subpopulation of IFN- superproducing T cells. Commitment to IFN- production through IL-18 was independent of NK cells and IL-12 but dependent on host-derived IFN-. To determine how expansion of these effectors occurred, IL-18 was shown to induce OX40L on dendritic cells, whereas peptide stimulation induced CD134 (OX40) on specific T cells. CD134 blockade inhibited T cell effector expansion thereby reducing the number of IFN- superproducers by 12-fold. Thus, independent of IL-12, IL-18 impacts T cell immunity throughout lymphoid and nonlymphoid tissue by bridging the innate and adaptive arms of the immune system through IFN- and the CD134 costimulatory pathway.

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