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Augmentation of Cutaneous Immune Responses by ATPS: Purinergic Agonists Define a Novel Class of Immunologic Adjuvants¹

Richard D. Granstein^2,*, Wanhong Ding^*, Jing Huang^*, Aton Holzer^*, Richard L. Gallo, Anna Di Nardo and John A. Wagner

Departments of^* Dermatology and Neurology and Neurosciences, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021; and Department of Medicine, University of California-San Diego, La Jolla, CA 92093

Extracellular nucleotides activate ligand-gated P2XR ion channels and G protein-coupled P2YRs. In this study we report that intradermal administration of ATPS, a hydrolysis-resistant P2 agonist, results in an enhanced contact hypersensitivity response in mice. Furthermore, ATPS enhanced the induction of delayed-type hypersensitivity to a model tumor vaccine in mice and enhanced the Ag-presenting function of Langerhans cells (LCs) in vitro. Exposure of a LC-like cell line to ATPS in the presence of LPS and GM-CSF augmented the induction of I-A, CD80, CD86, IL-1, and IL-12 p40 while inhibiting the expression of IL-10, suggesting that the immunostimulatory activities of purinergic agonists in the skin are mediated at least in part by P2Rs on APCs. In this regard, an LC-like cell line was found to express mRNA for P2X₁, P2X₇, P2Y₁, P2Y₂, P2Y₄, P2Y₉, and P2Y₁₁ receptors. We suggest that ATP, when released after trauma or infection, may act as an endogenous adjuvant to enhance the immune response, and that P2 agonists may augment the efficacy of vaccines.

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