• 中國醫(yī)科大學(xué)附屬第四醫(yī)院外科(遼寧沈陽 110032);

目的探討CD4+CD25+調(diào)節(jié)性T細(xì)胞在維持小鼠肝臟移植免疫耐受狀態(tài)中的作用。方法進行小鼠原位肝臟移植，誘導(dǎo)出移植免疫耐受后，向受體注射抗CD25抗體(PC61)以去除CD4+CD25+T細(xì)胞，檢測受體內(nèi)CD4+CD25+T細(xì)胞數(shù)量及叉狀頭/翅膀狀螺旋轉(zhuǎn)錄因子(Foxp3)的表達以確定CD4+CD25+T細(xì)胞完全被清除，同時觀察受體生存時間。結(jié)果與同種同系小鼠肝臟移植結(jié)果相似，同種異系肝臟移植小鼠的生存時間亦均超過70 d。移植免疫耐受誘導(dǎo)后，PC61不同注射方案均能完全去除受體小鼠肝臟、脾臟及血液中的CD4+CD25+T細(xì)胞，且移植肝臟中Foxp3 mRNA的表達也明顯降低，表明完全去除了CD4+CD25+調(diào)節(jié)性T細(xì)胞，但肝臟移植動物生存時間并未受到影響。結(jié)論CD4+CD25+調(diào)節(jié)性T細(xì)胞對于小鼠肝臟移植自發(fā)性免疫耐受的維持并非必需。

引用本文： 姜曉峰,王學(xué)范,崔哲銘,朱磊,郭大偉,孫文郁,林琳,唐裕福,梁健. CD4+CD25+調(diào)節(jié)性T細(xì)胞在維持小鼠肝臟移植自發(fā)性免疫耐受狀態(tài)中的作用. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(4): 366-369. doi: 復(fù)制

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6. Harada M, Seino K, Wakao H, et al. Downregulation of the invariant Valpha14 antigen receptor in NKT cells upon activation [J]. Int Immunol, 2004, 16(2): 241247.
7. Roncarolo MG, Battaglia M. Regulatory Tcell immunotherapy for tolerance to self antigens and alloantigens in humans [J]. Nat Rev Immunol, 2007, 7(8): 585598.
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11. Webster KE, Walters S, Kohler RE, et al. In vivo expansion of T reg cells with IL2mAb complexes: induction of resistance to EAE and longterm acceptance of islet allografts without immunosuppression [J]. J Exp Med, 2009, 206(4): 751760.
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13. Kearley J, Robinson DS, Lloyd CM. CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling [J]. J Allergy Clin Immunol, 2008, 122(3): 617624.
14. Curiel TJ. Tregs and rethinking cancer immunotherapy [J]. J Clin Invest, 2007, 117(5): 11671174.
15. Morse MA, Hobeika AC, Osada T, et al. Depletion of human regulatory T cells specifically enhances antigenspecific immune responses to cancer vaccines [J]. Blood, 2008, 112(3): 610618.
16. Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease [J]. Nat Immunol, 2005, 6(4): 353360.
17. Xue F, Chen W, Wang X, et al. Regulatory T cells contribute to the immunoregulatory effect on graft versus host reaction after liver transplantation in donordominant oneway MHC matching rats [J]. Transpl Immunol, 2009, 20(4): 232237.
18. Nguyen VH, Shashidhar S, Chang DS, et al. The impact of regulatory T cells on Tcell immunity following hematopoietic cell transplantation [J]. Blood, 2008, 111(2): 945953.
19. Kang SM, Tang Q, Bluestone JA. CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects [J]. Am J Transplant, 2007, 7(6): 14571463.
20. Iwami D, Zhang Q, Aramaki O, et al. Purified eicosapentaenoic acid induces prolonged survival of cardiac allografts and generates regulatory T cells [J]. Am J Transplant, 2009, 9(6): 12941307.
21. Yoshizawa A, Ito A, Li Y, et al. The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation [J]. Transplant Proc, 2005, 37(1): 3739.
22. Takatsuki M, Uemoto S, Inomata Y, et al. Weaning of immunosuppression in living donor liver transplant recipients [J]. Transplantation, 2001 , 72(3): 449454.
23. Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3dependent programme of regulatory Tcell differentiation [J]. Nature, 2007, 445(7129): 771775.
  1. 1. Sugioka A, Morita M, Fujita J, et al. Graft acceptance and tolerance induction in mouse liver transplantation using wild mice [J]. Transplant Proc, 2001, 33(12): 137139.
  2. 2. Joffre O, Santolaria T, Calise D, et al. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes [J]. Nat Med, 2008, 14(1): 8892.
  3. 3. Jiang X, Sun W, Guo D, et al. Cardiac allograft acceptance induced by blockade of CD40CD40L costimulation is dependent on CD4(+)CD25(+) regulatory T cells [J]. Surgery, 2011, 149(3): 336346.
  4. 4. Waldmann H, Graca L, Cobbold S, et al. Regulatory T cells and organ transplantation [J]. Semin Immunol, 2004, 16(2): 119126.
  5. 5. Sugioka A, Morita M, Esaki T, et al. Evaluation of microchimerism after orthotopic liver transplantation between allogeneic mice [J]. Transplant Proc, 1997, 29(12): 11891192.
  6. 6. Harada M, Seino K, Wakao H, et al. Downregulation of the invariant Valpha14 antigen receptor in NKT cells upon activation [J]. Int Immunol, 2004, 16(2): 241247.
  7. 7. Roncarolo MG, Battaglia M. Regulatory Tcell immunotherapy for tolerance to self antigens and alloantigens in humans [J]. Nat Rev Immunol, 2007, 7(8): 585598.
  8. 8. Trzonkowski P, Szaryńska M, My＇sliwska J, et al. Ex vivo expansion of CD4(+)CD25(+) T regulatory cells for immunosuppressive therapy [J]. Cytometry A, 2009, 75(3): 175188.
  9. 9. Tarbell KV, Yamazaki S, Steinman RM. The interactions of dendritic cells with antigenspecific, regulatory T cells that suppress autoimmunity [J]. Semin Immunol, 2006, 18(2): 93102.
  10. 10. Sakaguchi S. Naturally arising Foxp3expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and nonself [J]. Nat Immunol, 2005, 6(4): 345352.
  11. 11. Webster KE, Walters S, Kohler RE, et al. In vivo expansion of T reg cells with IL2mAb complexes: induction of resistance to EAE and longterm acceptance of islet allografts without immunosuppression [J]. J Exp Med, 2009, 206(4): 751760.
  12. 12. Pandiyan P, Zheng L, Ishihara S, et al. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivationmediated apoptosis of effector CD4+ T cells [J]. Nat Immunol, 2007, 8(12): 13531362.
  13. 13. Kearley J, Robinson DS, Lloyd CM. CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling [J]. J Allergy Clin Immunol, 2008, 122(3): 617624.
  14. 14. Curiel TJ. Tregs and rethinking cancer immunotherapy [J]. J Clin Invest, 2007, 117(5): 11671174.
  15. 15. Morse MA, Hobeika AC, Osada T, et al. Depletion of human regulatory T cells specifically enhances antigenspecific immune responses to cancer vaccines [J]. Blood, 2008, 112(3): 610618.
  16. 16. Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease [J]. Nat Immunol, 2005, 6(4): 353360.
  17. 17. Xue F, Chen W, Wang X, et al. Regulatory T cells contribute to the immunoregulatory effect on graft versus host reaction after liver transplantation in donordominant oneway MHC matching rats [J]. Transpl Immunol, 2009, 20(4): 232237.
  18. 18. Nguyen VH, Shashidhar S, Chang DS, et al. The impact of regulatory T cells on Tcell immunity following hematopoietic cell transplantation [J]. Blood, 2008, 111(2): 945953.
  19. 19. Kang SM, Tang Q, Bluestone JA. CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects [J]. Am J Transplant, 2007, 7(6): 14571463.
  20. 20. Iwami D, Zhang Q, Aramaki O, et al. Purified eicosapentaenoic acid induces prolonged survival of cardiac allografts and generates regulatory T cells [J]. Am J Transplant, 2009, 9(6): 12941307.
  21. 21. Yoshizawa A, Ito A, Li Y, et al. The roles of CD25+CD4+ regulatory T cells in operational tolerance after living donor liver transplantation [J]. Transplant Proc, 2005, 37(1): 3739.
  22. 22. Takatsuki M, Uemoto S, Inomata Y, et al. Weaning of immunosuppression in living donor liver transplant recipients [J]. Transplantation, 2001 , 72(3): 449454.
  23. 23. Gavin MA, Rasmussen JP, Fontenot JD, et al. Foxp3dependent programme of regulatory Tcell differentiation [J]. Nature, 2007, 445(7129): 771775.