Augmentation of cutaneous immune responses by ATP gamma S: purinergic agonists define a novel class of immunologic adjuvants.
Extracellular nucleotides activate ligand-gated P2XR ion channels and G protein-coupled P2YRs. In this study we report that intradermal administration of ATPgammaS, a hydrolysis-resistant P2 agonist, results in an enhanced contact hypersensitivity response in mice. Furthermore, ATPgammaS 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 ATPgammaS in the presence of LPS and GM-CSF augmented the induction of I-A, CD80, CD86, IL-1beta, 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 P2X(1), P2X(7), P2Y(1), P2Y(2), P2Y(4), P2Y(9), and P2Y(11) 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.
Granstein
Richard D
RD
Department of Dermatology, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY 10021, USA. rdgranst@med.cornell.edu
Ding
Wanhong
W
Huang
Jing
J
Holzer
Aton
A
Gallo
Richard L
RL
Di Nardo
Anna
A
Wagner
John A
JA
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000145:classification* / Q000627:therapeutic use; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D002460:Cell Line; D002999:Clone Cells; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger / Q000096:biosynthesis; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D058910:Purinergic P2 Receptor Agonists; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D016753:Interleukin-10; D018664:Interleukin-12; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate