Secretion of IL-2 and IFN-γ, But Not IL-4, by Antigen-Specific T Cells Requires Extracellular ATP
| Autor: | Kenneth E. Dombrowski, Heather P. Langston, Judith A. Kapp, Andrew T. Gewirtz, Yong Ke |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
Intracellular Fluid Adenosine T cell Immunology Epitopes T-Lymphocyte Mice Transgenic Biology Lymphocyte Activation Calcium in biology Cell Line Interferon-gamma Mice Adenosine Triphosphate Antigens CD T-Lymphocyte Subsets ATP hydrolysis Extracellular medicine Animals Immunology and Allergy V-ATPase Secretion Interphase Interleukin 4 Adenosine Triphosphatases Mice Inbred BALB C Binding Sites Hybridomas Apyrase Molecular biology Cell biology Mice Inbred C57BL medicine.anatomical_structure Gene Expression Regulation Cytokines Interleukin-2 Calcium Female Interleukin-4 Signal transduction Extracellular Space |
| Zdroj: | The Journal of Immunology. 170:2962-2970 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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 is expressed by activated lymphocytes. We have previously shown that nonhydrolyzable ATP analogs block the lytic activity of NK cells and CD8+ T cells as well as their E-NTPDase activity. These results suggest that the hydrolysis of ATP may play a role in lymphocyte function. Here we report that E-NTPDase activity is up-regulated within 15 min of T cell stimulation and that reversible and irreversible enzyme inhibitors profoundly reduce secretion of IL-2 and IFN-γ, but not IL-4. TNF-α, IL-10, and IL-5 production showed intermediate sensitivity to these ATP analogs. Depletion of extracellular ATP also inhibited secretion of IFN-γ, but not IL-4, supporting the interpretation that extracellular ATP is required for secretion of some, but not all, cytokines. E-NTPDase antagonists reduced transcription of IL-2 mRNA and inhibited TCR-mediated intracellular calcium flux. These results suggest that extracellular ATP plays an essential role in the TCR-mediated signal transduction cascade for expression of certain cytokine genes. |
| Databáze: | OpenAIRE |
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