Activation of Adenosine 2A Receptor Inhibiting Rat T Cell Function in Vitro_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Jianfei ¹ , TANG Liming ¹ , WANG Feng ² , LU Huahu ² , REN Jun. ¹

1.Department of General Surgery, Changzhou No.2 Hospital Affiliated of Nanjing Medical University, Changzhou 213003, Jiangsu Province, China;;
2.Liver Transplant Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;

Corresponding author：

Keywords：

Adenosine receptor; T cell activation; T cell proliferation; Cytotoxic effect

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Objective To study the effects of adenosine 2A receptor activation on activation, proliferation, and toxicity of T lymphocytes stimulated by phytohemagglutinin (PHA) in vitro. Methods A model of activated T cells was established by stimulating the cells with PHA. Those T cells were treated with different concentrations of adenosine 2A receptors agonist (0.01 μmol/L, 0.1 μmol/L, 1 μmol/L, and 10 μmol/L CGS21680). The expressions of CD69, CD25 and proliferation of T cells were measured by fluorescent antibody stain and flow cytometry. ELISA method was used to detect IL-2 and INF-γ levels. Results All concentrations of CGS21680 significantly inhibited the expressions of CD25 and CD69 on PHA-stimulated T cells surface and proliferation of T cells （P lt;0.05， P lt;0.01）. IL-2 and INF-γ secreted by T cells were significantly suppressed, too （P lt;0.01）. Conclusion Activation of adenosine 2A receptor can effectively inhibit the activation, proliferation, and toxicity of T cells in vitro.

Citation： ZHU Jianfei,TANG Liming,WANG Feng,LU Huahu,REN Jun.. Activation of Adenosine 2A Receptor Inhibiting Rat T Cell Function in Vitro. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(11): 1136-1140. doi: Copy

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8.	Luijk B, van den Berge M, Kerstjens HA, et al. Effect of an inhaled adenosine A2A agonist on the allergen-induced late asthmatic response [J]. Allergy, 2008; 63(1): 75-80.
9.	Grenz A, Baier D, Petroktistis F, et al. Theophylline improves early allograft function in rat kidney transplantation [J]. J Pharmacol Exp Ther, 2006; 317(2): 473-479.
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21.	Carrizosa E, Gomez TS, Labno CM, et al. Hematopoietic lineage cell-specific protein 1 is recruited to the immunological synapse by IL-2-inducible T cell kinase and regulates phospholipase Cgamma1 Microcluster dynamics during T cell spreading [J]. J Immunol, 2009; 183(11): 7352-7761.
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23.	Yamamoto S, Yamamoto T, Kataoka T, et al. Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN 〔correction of INF〕 and augment IFN-mediated 〔correction of INF〕 natural killer activity [J]. J Immunol, 1992; 148(12): 4072-4076.
24.	Gallin M, Edmonds K, Ellner JJ, et al. Cell-mediated immune responses in human infection with Onchocerca volvulus [J]. J Immunol, 1988; 140(6): 1999-2007.
25.	Niessner A, Sato K, Chaikof EL, et al. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha [J]. Circulation, 2006; 114(23): 2482-2489.

1. Zarek PE, Huang CT, Lutz ER, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells [J]. Blood, 2008; 111(1): 251-259.
2. Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in small-for-size liver transplantation [J]. Transpl Int, 2007; 20(1): 93-101.
3. Tan EY, Richard CL, Zhang H, et al. Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway [J]. Am J Physiol Cell Physiol, 2006; 291(3): C433-C444.
4. Liang X, Yu JJ, Reed E. Protein phosphatase 2A interacts with Chk2 and regulates its phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells [A]. AACR Meeting Abstracts. Anaheim, CA, 2005: 1309.
5. Liang X, Reed E, Yu JJ. Caffeine enhances cisplatin-induced phosphorylation of Chk 2 at Thr-68 via inhibition of adenosine receptor signaling in ovarian cancer cells [A]. AACR Meeting Abstracts. Orlando, Florida, 2004: 605.
6. Lau CL, Zhao Y, Kron IL, et al. The role of adenosine A2A receptor signaling in bronchiolitis obliterans [J]. Ann Thorac Surg, 2009; 88(4): 1071-1078.
7. Csóka B, Németh ZH, Virág L, et al. A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli [J]. Blood, 2007; 110(7): 2685-2695.
8. Luijk B, van den Berge M, Kerstjens HA, et al. Effect of an inhaled adenosine A2A agonist on the allergen-induced late asthmatic response [J]. Allergy, 2008; 63(1): 75-80.
9. Grenz A, Baier D, Petroktistis F, et al. Theophylline improves early allograft function in rat kidney transplantation [J]. J Pharmacol Exp Ther, 2006; 317(2): 473-479.
10. Reece TB, Ellman PI, Maxey TS, et al. Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation [J]. J Thorac Cardiovasc Surg, 2005; 129(5): 1137-1143.
11. Varani K, Laghi-Pasini F, Camurri A, et al. Changes of peripheral A2A adenosine receptors in chronic heart failure and cardiac transplantation [J]. FASEB J, 2003; 17(2): 280-282.
12. Lappas CM, Liu PC, Linden J, et al. Adenosine A2A receptor activation limits graft-versus-host disease after allogenic hematopoietic stem cell transplantation [J]. J Leukoc Biol, 2010; 87(2): 345-354.
13. Schmitz ML, Bacher S, Dienz O. NF-kappaB activation pathways induced by T cell costimulation [J]. FASEB J, 2003; 17(15): 2187-2193.
14. Hughes K, Edin S, Antonsson A, et al. Calmodulin-dependent kinase Ⅱ mediates T cell receptor/CD3- and phorbol ester-induced activation of IkappaB kinase [J]. J Biol Chem, 2001; 276(38): 36008-36013.
15. Pule MA, Straathof KC, Dotti G, et al. Three-module signaling endo-domain artifical T-cell receptor which transmits CD28, OX40 and CD3-zeta signals enhances IL-2 release and proliferative response in transduced primary T-cells [J]. Blood (ASH Annual Meeting Abstracts), 2004; 104(11): 1747.
16. Srinivasan S, Bolick DT, Lukashev D, et al. Sphingosine-1-phosphate reduces CD4+ T-cell activation in type 1 diabetes through regulation of hypoxia-inducible factor short isoform I.1 and CD69 [J]. Diabetes, 2008; 57(2): 484-493.
17. Hermann-Kleiter N, Thuille N, Pfeifhofer C, et al. PKCtheta and PKA are antagonistic partners in the NF-AT transactivation pathway of primary mouse CD3+ T lymphocytes [J]. Blood, 2006; 107(12): 4841-4848.
18. Nakamura K, Kitani A, Fuss I, et al. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice [J]. J Immunol, 2004; 172(2): 834-842.
19. Oppenheim JJ. IL-2: more than a T cell growth factor [J]. J Immunol, 2007; 179(3): 1413-1414.
20. Santoli D, Clark SC, Kreider BL, et al. Amplification of IL-2-driven T cell proliferation by recombinant human IL-3 and granulocyte-macrophage colony-stimulating factor [J]. J Immunol, 1988; 141(2): 519-526.
21. Carrizosa E, Gomez TS, Labno CM, et al. Hematopoietic lineage cell-specific protein 1 is recruited to the immunological synapse by IL-2-inducible T cell kinase and regulates phospholipase Cgamma1 Microcluster dynamics during T cell spreading [J]. J Immunol, 2009; 183(11): 7352-7761.
22. Erdmann AA, Gao ZG, Jung U, et al. Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo [J]. Blood, 2005; 105(12): 4707-4714.
23. Yamamoto S, Yamamoto T, Kataoka T, et al. Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN 〔correction of INF〕 and augment IFN-mediated 〔correction of INF〕 natural killer activity [J]. J Immunol, 1992; 148(12): 4072-4076.
24. Gallin M, Edmonds K, Ellner JJ, et al. Cell-mediated immune responses in human infection with Onchocerca volvulus [J]. J Immunol, 1988; 140(6): 1999-2007.
25. Niessner A, Sato K, Chaikof EL, et al. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha [J]. Circulation, 2006; 114(23): 2482-2489.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Activation of Adenosine 2A Receptor Inhibiting Rat T Cell Function in Vitro

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