Secretion of IL-2 and IFN-γ, But Not IL-4, by Antigen-Specific T Cells Requires Extracellular ATP

作者: Heather P. Langston , Yong Ke , Andrew T. Gewirtz , Kenneth E. Dombrowski , Judith A. Kapp

DOI: 10.4049/JIMMUNOL.170.6.2962

关键词: V-ATPaseSignal transductionCalcium in biologyATP hydrolysisExtracellularCell biologyBiologyInterleukin 4T cellSecretionMolecular biologyImmunology

摘要: Extracellular ATP and other nucleotides transmit signals to cells via surface-associated molecules whose binding sites face the extracellular milieu. Ecto-nucleoside triphosphate diphosphohydrolase is such an ATP-binding enzyme that expressed by activated lymphocytes. We have previously shown nonhydrolyzable analogs block lytic activity of NK CD8+ T as well their E-NTPDase activity. These results suggest hydrolysis may play a role in lymphocyte function. Here we report up-regulated within 15 min cell stimulation reversible irreversible inhibitors profoundly reduce secretion IL-2 IFN-γ, but not IL-4. TNF-α, IL-10, IL-5 production showed intermediate sensitivity these analogs. Depletion also inhibited IL-4, supporting interpretation required for some, all, cytokines. antagonists reduced transcription mRNA TCR-mediated intracellular calcium flux. plays essential signal transduction cascade expression certain cytokine genes.

参考文章(59)
EF Tizzano, M Domenech, C Altisent, J Tusell, M Baiget, Inversions in the factor VIII gene in Spanish hemophilia A patients. Blood. ,vol. 83, pp. 3826- 3826 ,(1994) , 10.1182/BLOOD.V83.12.3826.3826
Kenneth E. Dombrowski, Yong Ke, Judith A. Kapp, Role of Ecto-ATPase in Lymphocyte Function Springer US. pp. 197- 207 ,(1997) , 10.1007/978-1-4615-5955-9_24
George R. Dubyak, Jeffrey S. Fedan, Biological Actions of Extracellular Atp ,(1991)
Ting-Fang Wang, Guido Guidotti, CD39 is an ecto-(Ca2+,Mg2+)-apyrase. Journal of Biological Chemistry. ,vol. 271, pp. 9898- 9901 ,(1996) , 10.1074/JBC.271.17.9898
Xavier Duhant, Liliane Schandené, Catherine Bruyns, Nathalie Suarez Gonzalez, Michel Goldman, Jean-Marie Boeynaems, Didier Communi, Extracellular Adenine Nucleotides Inhibit the Activation of Human CD4 + T Lymphocytes Journal of Immunology. ,vol. 169, pp. 15- 21 ,(2002) , 10.4049/JIMMUNOL.169.1.15
T F Gajewski, F W Fitch, S R Schell, Evidence implicating utilization of different T cell receptor-associated signaling pathways by TH1 and TH2 clones. Journal of Immunology. ,vol. 144, pp. 4110- 4120 ,(1990)
Gary S. Wood, Thomas F. Tedder, Geoffrey S. Kansas, Expression, distribution, and biochemistry of human CD39. Role in activation-associated homotypic adhesion of lymphocytes. Journal of Immunology. ,vol. 146, pp. 2235- 2244 ,(1991)
Herbert Zimmermann, Nucleotides and cd39: principal modulatory players in hemostasis and thrombosis. Nature Medicine. ,vol. 5, pp. 987- 988 ,(1999) , 10.1038/12419
U Beutner, A Zubiaga, B T Huber, E Muñoz, IL-1 activates two separate signal transduction pathways in T helper type II cells. Journal of Immunology. ,vol. 144, pp. 964- 969 ,(1990)