利用IDO的雙向作用重建肝移植后乙肝主動免疫的體外實驗_《中國普外基礎與臨床雜志》

作者：

陳永兵 ^1,2 , 于聰慧 ¹ , 巨邦律 ¹

1.中國人民解放軍北京軍區總醫院肝膽外科(北京 100700);;
2.中國人民解放軍總醫院肝膽外科（北京 100863）;

關鍵詞：

肝移植乙型病毒性肝炎吲哚胺2,3-二氧化酶免疫腺病毒

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目的觀察雙目的基因吲哚胺2,3二氧化酶(IDO)和乙型肝炎病毒前S抗原(HBV preS)在肝癌細胞株HepG2細胞的表達及其對人外周血淋巴細胞(PBLC)的抑制作用。方法將前期制備的重組腺病毒Ad-IDOEGFP-preS 轉染HepG2細胞，用倒置熒光顯微鏡觀察增強型綠色熒光蛋白(EGFP)的表達，RT-PCR檢測目的基因IDO和HBV preS mRNA的表達; 與人PBLC共培養，同位素標記法觀察IDO對其增殖的抑制作用。結果HepG2細胞在轉染3 d后即可見明顯的EGFP表達，7 d后熒光更強，提示目的基因已成功導入HepG2細胞。 RT-PCR顯示感染Ad-IDOEGFP-preS重組腺病毒的HepG2細胞中含有IDO和HBV preS基因片段，IDO相對表達強度為1.27，HBV preS相對表達強度為1.18，而對照組HepG2細胞未出現IDO和HBV preS基因片段。與其共培養的淋巴細胞每分鐘放射線計數(CPM)為(7 471±1 375)次/min，明顯低于對照組CPM 〔(13 821±1 997) 次/min〕，P lt;0.001。結論重組腺病毒Ad-IDOEGFP-preS能有效地將目的基因IDO和HBV preS導入HepG2細胞并表達，攜帶該基因的HepG2細胞對PBLC的增殖具有明顯的抑制作用，這將為進一步的肝移植乙肝主動免疫動物實驗奠定基礎。

引用本文： 陳永兵,于聰慧,巨邦律. 利用IDO的雙向作用重建肝移植后乙肝主動免疫的體外實驗. 中國普外基礎與臨床雜志, 2011, 18(2): 126-130. doi: 復制

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11.	O’Grady JG, Smith HM, Davies SE, et al. Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications [J]. J Hepatol, 1992, 14(1): 104111.
12.	Jiang L, Yan L, Li B, et al. Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized lowdose hepatitis B immunoglobulin [J]. Am J Transplant, 2010, 10(8): 18611869.
13.	Chen J, Yi L, Jia JD, et al. Hepatitis B immunoglobulins and/or lamivudine for preventing hepatitis B recurrence after liver transplantation: a systematic review [J]. J Gastroenterol Hepatol, 2010, 25(5): 872879.
14.	Jiang L, Jiang LS, Cheng NS, et al. Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation [J]. World J Gastroenterol, 2009, 15(20): 24892499.
15.	Strkel P, Stoffel M, Lerut J, et al. Response to an experimental HBV vaccine permits withdrawal of HBIg prophylaxis in fulminant and selected chronic HBVinfected liver graft recipients [J]. Liver Transpl, 2005, 11(10): 12281234.
16.	SánchezFueyo A, Rimola A, Grande L, et al. Hepatitis B immunoglobulion discontinunation followed by hepatitis B virus vaccine: A new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation [J]. Hepatology, 2000, 31(2): 496501.
17.	Tahara H, Tanaka Y, Ishiyama K, et al. Successful hepatitis B vaccination in liver transplant recipients with donorspecific hyporesponsiveness [J]. Transpl Int, 2009, 22(8): 805813.
18.	MabyEl Hajjami H, AméThomas P, Pangault C, et al. Functional alteration of the lymphoma stromal cell niche by the cytokine context: role of indoleamine2, 3 dioxygenase [J]. Cancer Res, 2009, 69(7): 32283237.
19.	Johnson BA 3rd, Kahler DJ, Baban B, et al. Blymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2, 3dioxygenase [J]. Proc Natl Acad Sci USA, 2010, 107(23): 1064410648.
20.	Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2, 3dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease [J]. Sci Transl Med, 2010, 2(32): 32ra36.
21.	Funeshima N, Fujino M, Kitazawa Y, et al. Inhibition of allogeneic Tcell responses by dendritic cells expressing transduced indoleamine 2, 3dioxygenase [J]. J Gene Med, 2005, 7(5): 565575.
22.	Bozza S, Fallarino F, Pitzurra L, et al. A crucial role for tryptophan catabolism at the host/Candida albicans interface [J]. J Immunol, 2005, 174(5): 29102918.
23.	Beutelspacher SC, Pillai R, Watson MP, et al. Function of indoleamine 2, 3dioxygenase in corneal allograft rejection and prolongation of allograft survival by overexpression [J]. Eur J Immunol, 2006, 36(3): 690700.
24.	Li Y, Tredget EE, Ghaffari A, et al. Local expression of indoleamine 2,3dioxygenase protects engraftment of xenogeneic skin substitute [J]. J Invest Dermatol, 2006, 126(1): 128136.
25.	孫星, 裘國強, 徐軍明, 等. 大鼠肝臟移植后的排斥反應與吲哚胺 2, 3 雙加氧酶基因的關系 [J]. 中華器官移植雜志, 2006, 27(7): 392395.
26.	Iwamoto N, Ito H, Ando K, et al. Upregulation of indoleamine 2,3dioxygenase in hepatocyte during acute hepatitis caused by hepatitis B virusspecific cytotoxic T lymphocytes in vivo [J]. Liver Int, 2009, 29(2): 277283.
27.	Wang Y, Jacob JR, Menne S, et al. Interferonγassociated responses to woodchuck hepatitis virus infection in neonatal woodchucks and virusinfected hepatocytes [J]. J Viral Hepat, 2004, 11(5): 404417.
28.	Narayan R, Buronfosse T, Schultz U, et al. Rise in γ interferon expression during resolution of duck hepatitis B virus infection [J]. J Gen Virol, 2006, 87(Pt 11): 32253232.
29.	Long JE, Huang LN, Qin ZQ, et al. IFNγ increases efficiency of DNA vaccine in protecting ducks against infection [J]. World J Gastroenterol, 2005, 11(32): 49674973.

1. Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences [J]. Antivir Ther, 2010, 15 Suppl 3: 2533.
2. Chae HB, Kim JH, Kim JK, et al. Current status of liver diseases in Korea: hepatitis B [J]. Korean J Hepatol, 2009, 15 Suppl 6: S13S24.
3. Raimondo G, Pollicino T, Romanò L, et al. A 2010 update on occult hepatitis B infection [J]. Pathol Biol (Paris), 2010, 58(4): 254257.
4. Beckebaum S, Sotiropoulos GC, Gerken G, et al. Hepatitis B and liver transplantation: 2008 update [J]. Rev Med Virol, 2009, 19(1): 729.
5. Fallahian F, Alavian SM, Fallahian V, et al. Impact of immunosuppression and chemotherapy on reactivation of viral hepatitis [J]. Saudi J Kidney Dis Transpl, 2010, 21(4): 621627.
6. Xie SB, Zhu JY, Ying Z, et al. Prevention and risk factors of the HBV recurrence after orthotopic liver transplantation: 160 cases followup study [J]. Transplantation, 2010, 90(7): 786790.
7. Sperl J, Franková S, Spicák J. Viral hepatitis in immunosuppressed patients [J]. Klin Mikrobiol Infekc Lek, 2010, 16(4): 120123.
8. Chen YB, Li SD, He YP, et al. Immunosuppressive effect of IDO on T cells in patients with chronic hepatitis B [J]. Hepatol Res, 2009, 39(5): 463468.
9. 陳永兵, 李斯丹, 龔建平. 吲哚胺2,3二氧化酶與慢性乙型肝炎的免疫重建 [J]. 中華肝臟病雜志, 2008, 16(2):157158.
10. Todo S, Demetris AJ, Van Thiel D, et al. Orthotopic liver transplantation for patients with hepatitis B virusrelated liver disease [J]. Hepatology, 1991, 13(4): 619626.
11. O’Grady JG, Smith HM, Davies SE, et al. Hepatitis B virus reinfection after orthotopic liver transplantation. Serological and clinical implications [J]. J Hepatol, 1992, 14(1): 104111.
12. Jiang L, Yan L, Li B, et al. Prophylaxis against hepatitis B recurrence posttransplantation using lamivudine and individualized lowdose hepatitis B immunoglobulin [J]. Am J Transplant, 2010, 10(8): 18611869.
13. Chen J, Yi L, Jia JD, et al. Hepatitis B immunoglobulins and/or lamivudine for preventing hepatitis B recurrence after liver transplantation: a systematic review [J]. J Gastroenterol Hepatol, 2010, 25(5): 872879.
14. Jiang L, Jiang LS, Cheng NS, et al. Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation [J]. World J Gastroenterol, 2009, 15(20): 24892499.
15. Strkel P, Stoffel M, Lerut J, et al. Response to an experimental HBV vaccine permits withdrawal of HBIg prophylaxis in fulminant and selected chronic HBVinfected liver graft recipients [J]. Liver Transpl, 2005, 11(10): 12281234.
16. SánchezFueyo A, Rimola A, Grande L, et al. Hepatitis B immunoglobulion discontinunation followed by hepatitis B virus vaccine: A new strategy in the prophylaxis of hepatitis B virus recurrence after liver transplantation [J]. Hepatology, 2000, 31(2): 496501.
17. Tahara H, Tanaka Y, Ishiyama K, et al. Successful hepatitis B vaccination in liver transplant recipients with donorspecific hyporesponsiveness [J]. Transpl Int, 2009, 22(8): 805813.
18. MabyEl Hajjami H, AméThomas P, Pangault C, et al. Functional alteration of the lymphoma stromal cell niche by the cytokine context: role of indoleamine2, 3 dioxygenase [J]. Cancer Res, 2009, 69(7): 32283237.
19. Johnson BA 3rd, Kahler DJ, Baban B, et al. Blymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2, 3dioxygenase [J]. Proc Natl Acad Sci USA, 2010, 107(23): 1064410648.
20. Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2, 3dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease [J]. Sci Transl Med, 2010, 2(32): 32ra36.
21. Funeshima N, Fujino M, Kitazawa Y, et al. Inhibition of allogeneic Tcell responses by dendritic cells expressing transduced indoleamine 2, 3dioxygenase [J]. J Gene Med, 2005, 7(5): 565575.
22. Bozza S, Fallarino F, Pitzurra L, et al. A crucial role for tryptophan catabolism at the host/Candida albicans interface [J]. J Immunol, 2005, 174(5): 29102918.
23. Beutelspacher SC, Pillai R, Watson MP, et al. Function of indoleamine 2, 3dioxygenase in corneal allograft rejection and prolongation of allograft survival by overexpression [J]. Eur J Immunol, 2006, 36(3): 690700.
24. Li Y, Tredget EE, Ghaffari A, et al. Local expression of indoleamine 2,3dioxygenase protects engraftment of xenogeneic skin substitute [J]. J Invest Dermatol, 2006, 126(1): 128136.
25. 孫星, 裘國強, 徐軍明, 等. 大鼠肝臟移植后的排斥反應與吲哚胺 2, 3 雙加氧酶基因的關系 [J]. 中華器官移植雜志, 2006, 27(7): 392395.
26. Iwamoto N, Ito H, Ando K, et al. Upregulation of indoleamine 2,3dioxygenase in hepatocyte during acute hepatitis caused by hepatitis B virusspecific cytotoxic T lymphocytes in vivo [J]. Liver Int, 2009, 29(2): 277283.
27. Wang Y, Jacob JR, Menne S, et al. Interferonγassociated responses to woodchuck hepatitis virus infection in neonatal woodchucks and virusinfected hepatocytes [J]. J Viral Hepat, 2004, 11(5): 404417.
28. Narayan R, Buronfosse T, Schultz U, et al. Rise in γ interferon expression during resolution of duck hepatitis B virus infection [J]. J Gen Virol, 2006, 87(Pt 11): 32253232.
29. Long JE, Huang LN, Qin ZQ, et al. IFNγ increases efficiency of DNA vaccine in protecting ducks against infection [J]. World J Gastroenterol, 2005, 11(32): 49674973.

《中國普外基礎與臨床雜志》

利用IDO的雙向作用重建肝移植后乙肝主動免疫的體外實驗

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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《中國普外基礎與臨床雜志》

利用IDO的雙向作用重建肝移植后乙肝主動免疫的體外實驗

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料