移植排斥治療中不同免疫抑制劑對調節性T細胞活化及功能的影響：結合基礎和臨床的系統評價△_《中國循證醫學雜志》

作者：

張春桃 ¹ , 單娟 ¹ , 馮莉 ¹ , 盧俊 ¹ , 肖政 ¹ , 羅蕾 ¹ , 李成文 ¹ , 郭穎嘉 ¹ ,  李幼平 ^1,2

1. 四川大學華西醫院衛生部移植工程與移植免疫重點實驗室（成都 610041）； 2. 四川大學華西醫院中國循證醫學中心（成都 610041）;

關鍵詞：

CD4+CD25+調節性T細胞免疫抑制劑系統評價

DOI：

10.7507/1672-2531.20100485

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　系統評價不同免疫抑制劑對調節性T細胞活化及功能的影響。
方法　計算機檢索Cochrane Library（2009年第4期）、MEDLINE（1966～2009.11）和EMbase（1980～2009.11），收集所有相關臨床和基礎研究。以移植受者外周血調節性T細胞含量、急排發生率、移植物功能作為臨床研究的分析指標；以調節性T細胞的增殖活性、抑制活性、表型及可能機制作為基礎研究的分析指標分析納入文獻并進行方法學評價及數據分析。
結果　共納入42篇文獻，其中臨床研究19篇，基礎研究23篇。涉及的免疫抑制劑有CNI、Rapa、MMF、IL-2受體阻斷抗體、共刺激通路封閉抗體、T細胞清除抗體；主要集中在CNI和Rapa兩類免疫抑制劑上。8個關于Rapa與CNI比較的基礎研究顯示：Rapa能夠增強調節性T細胞的增殖活性及抑制功能，而CNI則會抑制其增殖。5個關于Rapa與CNI比較的臨床研究（共158例腎移植受者）顯示：Rapa組移植受者外周血調節性T細胞含量高于CNI組，但兩組間隨訪6～42個月移植物功能無明顯差異。
結論　 Rapa能夠增強調節性T細胞的增殖活性及功能，但增加的調節性T細胞與移植物功能間并未顯示出相關性，這不排除是樣本量少和隨訪時間短引起的偏倚。因此，還需要更多大樣本長時間的高質量研究以證實或否定上述結論。

引用本文： 張春桃,單娟,馮莉,盧俊,肖政,羅蕾,李成文,郭穎嘉,李幼平. 移植排斥治療中不同免疫抑制劑對調節性T細胞活化及功能的影響：結合基礎和臨床的系統評價△. 中國循證醫學雜志, 2010, 10(6): 740-748. doi: 10.7507/1672-2531.20100485 復制

1.	Lechler RI, Sykes M, Thomson AW, et al. Organ transplantation-how much of the promise has been realized? Nat Med, 2005, 11(6): 605-613.
2.	Lukes DJ, Herlenius G, Rizell M, et al. Late mortality in. 679 consecutive liver transplant recipients: the Gothenburg liver transplant experience. Transplant Proc, 2006, 38(8): 2671-2672.
3.	Puig N, de la Rubia J, Remigia MJ, et al. Morbidity and transplant-related mortality of CBV and BEAM preparative regimens for patients with lymphoid malignancies undergoing autologous stem-cell transplantation. Leuk Lymphoma, 2006, 47(8): 1488-1494.
4.	Sykes M. Immune tolerance: mechanisms and application in clinical transplantation. J Intern Med, 2007, 262(3): 288-310.
5.	Xia G, Shah M, Luo X. Prevention of allograft rejection by amplification of Foxp3+CD4+CD25+ regulatory T cells. Transl Res, 2009, 153(2): 60-70.
6.	Joffre O, Santolaria T, Calise D, et al. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat Med, 2008, 14(1): 88-92.
7.	Meloni F, Vitulo P, Bianco AM, et al. Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: Correlation with transplant outcome. Transplantation, 2004, 77(5): 762-766.
8.	Louis S, Braudeau C, Giral M, et al. Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. Transplantation, 2006, 81(3): 398-407.
9.	Daniel V, Naujokat C, Sadeghi M, et al. Observational support for an immunoregulatory role of CD3+CD4+CD25+IFN-gamma+ blood lymphocytes in kidney transplant recipients with good long-term graft outcome. Transpl Int, 2008, 21(7): 646-660.
10.	Akl A, Jones ND, Rogers N, et al. An investigation to assess the potential of CD25highCD4+ T cells to regulate responses to donor alloantigens in clinically stable renal transplant recipients. Transpl Int, 2008, 21(1): 65-73.
11.	Jia LY, Yuan BB, Wang J, et al. Methods of Systematic Review of Health Policy Researches. Chin J Evid-Based Med, 2009, 9(10): 1037-1043.
12.	Gregori S, Casorati M, Amuchastegui S, et al. Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol, 2001, 167(4): 1945-1953.
13.	Chiffoleau E, Bériou G, Dutartre P, et al. Role for thymic and splenic regulatory CD4+ T cells induced by donor dendritic cells in allograft tolerance by LF15-0195 treatment. J Immunol, 2002, 168(10): 5058-5069.
14.	Baan CC, van der Mast BJ, Klepper M, et al. Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation, 2005, 80(1): 110-117.
15.	Demirkiran A, Kok A, Kwekkeboom J, et al. Decrease of CD4+CD25+ T cells in peripheral blood after liver transplantation: association with immunosuppression. Transplant Proc, 2005, 37(2): 1194-1196.
16.	Tang W, Yang Y, Zhang F, et al. Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells. Int Immunopharmacol, 2005, 5(13-14): 1904-1913.
17.	Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood, 2005, 105(12): 4743-4748.
18.	Wang H, Zhao L, Sun Z, et al. A potential side effect of cyclosporin A: inhibition of CD4(+)CD25(+) regulatory T cells in mice. Transplantation, 2006, 82(11): 1484-1492.
19.	Li W, Carper K, Liang Y, et al. Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance. Transplant Proc, 2006,38(10): 3207-3208.
20.	San Segundo D, Ruiz JC, Fernández-Fresnedo G, et al. Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients. Transplant Proc, 2006, 38(8): 2391-2393.
21.	Coenen JJ, Koenen HJ, van Rijssen E, et al. Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood, 2006, 107(3): 1018-1023.
22.	Chavez H, Beaudreuil S, Abbed K, et al. Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade. Transpl Immunol, 2007, 17(4): 243-248.
23.	Ardalan MR, Maljaei H, Shoja MM, et al. Calcitriol started in the donor, expands the population of CD4+CD25+ T cells in renal transplant recipients. Transplant Proc, 2007, 39(4): 951-953.
24.	Lim DG, Joe IY, Park YH, et al. Effect of immunosuppressants on the expansion and function of naturally occurring regulatory T cells. Transpl Immunol, 2007, 18(2): 94-100.
25.	Kreijveld E, Koenen HJ, Klasen IS, et al. Following anti-CD25 treatment, a functional CD4+CD25+ regulatory T-cell pool is present in renal transplant recipients. Am J Transplant, 2007, 7(1): 249-255.
26.	Kopf H, de la Rosa GM, Howard OM, et al. Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int Immunopharmacol, 2007, 7(13): 1819-1824.
27.	Coenen JJ, Koenen HJ, van Rijssen E, et al. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+ CD25+ FoxP3+ T cells. Bone Marrow Transplant, 2007, 39(9): 537-545.
28.	San Segundo D, Fábrega E, López-Hoyos M, et al. Reduced numbers of blood natural regulatory T cells in stable liver transplant recipients with high levels of calcineurin inhibitors. Transplant Proc, 2007, 39(7): 2290-2292.
29.	Noris M, Casiraghi F, Todeschini M, et al. Regulatory T cells and T cell depletion: role of immunosuppressive drugs. J Am Soc Nephrol, 2007, 18(3): 1007-1018.
30.	Ruggenenti P, Perico N, Gotti E, et al. Sirolimus versus cyclosporine therapy increases circulating regulatory T cells, but does not protect renal transplant patients given alemtuzumab induction from chronic allograft injury. Transplantation, 2007, 84(8): 956-964.
31.	Qu Y, Zhang B, Zhao L, et al. The effect of immunosuppressive drug rapamycin on regulatory CD4+CD25+Foxp3+T cells in mice. Transpl Immunol, 2007, 17(3): 153-161.
32.	Korczak-Kowalska G, Wierzbicki P, Bocian K, et al. The influence of immuosuppressive therapy on the development of CD4+CD25+ T cells after renal transplantation. Transplant Proc, 2007, 39(9): 2721-2723.
33.	Kreijveld E, Koenen HJ, Hilbrands LB, et al. The immunosuppressive drug FK778 induces regulatory activity in stimulated human CD4+ CD25- T cells. Blood, 2007, 109(1): 244-252.
34.	Morales J, Bono MR, Fierro A, et al. Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells. Transplant Proc, 2008, 40(9): 3223-3228.
35.	Pascual J, Bloom D, Torrealba J, et al. Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab: clinical outcomes and effect on T-regulatory cells. Am J Transplant, 2008, 8(7): 1529-1536.
36.	Bloom DD, Chang Z, Fechner JH, et al. CD4+ CD25+ FOXP3+ regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am J Transplant, 2008, 8(4): 793-802.
37.	Long SA, Buckner JH. Combination of rapamycin and IL-2 increases de novo induction of human CD4(+)CD25(+)FOXP3(+) T cells. J Autoimmun, 2008, 30(4): 293-302.
38.	Liu Y, Chen Y, Liu FQ, et al. Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation. Transpl Int, 2008, 21(5): 483-494.
39.	Yi H, Zhen Y, Zeng C, et al. Depleting anti-CD4 monoclonal antibody (GK1.5) treatment: influence on regulatory CD4+CD25+Foxp3+ T cells in mice. Transplantation, 2008, 85(8): 1167-1174.
40.	Meng L, Wu Z, Wang Y, et al. Differential impact of CD154 costimulation blockade on alloreactive effector and regulatory T cells in murine renal transplant recipients. Transplantation, 2008, 85(9): 1332-1338.
41.	Liu Z, Fang Y, Wang X, et al. Upregulation of molecules associated with T-regulatory function by thymoglobulin pretreatment of human CD4+ cells. Transplantation, 2008, 86(10): 1419-1426.
42.	Bluestone JA, Liu W, Yabu JM, et al. The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am J Transplant, 2008, 8(10): 2086-2096.
43.	Zeiser R, Leveson-Gower DB, Zambricki EA, et al. Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells. Blood, 2008, 111(1): 453-462.
44.	Wang Z, Xiao L, Shi BY, et al. Short-term anti-CD25 monoclonal antibody treatment and neogenetic CD4(+)CD25(high) regulatory T cells in kidney transplantation. Transpl Immunol, 2008, 19(1): 69-73.
45.	Hendrikx TK, Velthuis JH, Klepper M, et al. Monotherapy rapamycin allows an increase of CD4 CD25 FoxP3 T cells in renal recipients. Transpl Int, 2009, 22(9): 884-891.
46.	Calvo-Turrubiartes M, Romano-Moreno S, García-Hernández M, et al. Quantitative analysis of regulatory T cells in kidney graft recipients: a relationship with calcineurin inhibitor level. Transpl Immunol, 2009, 21(1): 43-49.
47.	Demirkiran A, Sewgobind VD, van der Weijde J, et al. Conversion from calcineurin inhibitor to mycophenolate mofetil-based immunosuppression changes the frequency and phenotype of CD4+FOXP3+ regulatory T cells. Transplantation, 2009, 87(7): 1062-1068.
48.	Levitsky J, Miller J, Wang E, et al. Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents. Hum Immunol, 2009, 70(3): 146-150.
49.	Singh AK, Horvath KA, Mohiuddin MM. Rapamycin promotes the enrichment of CD4(+)CD25(hi)FoxP3(+) T regulatory cells from na?ve CD4(+) T cells of baboon that suppress antiporcine xenogenic response in vitro. Transplant Proc, 2009, 41(1): 418-421.
50.	Javeed A, Zhang B, Qu Y, et al. The significantly enhanced frequency of functional CD4+CD25+Foxp3+ T regulatory cells in therapeutic dose aspirin-treated mice. Transpl Immunol, 2009, 20(4): 253-260.

1. Lechler RI, Sykes M, Thomson AW, et al. Organ transplantation-how much of the promise has been realized? Nat Med, 2005, 11(6): 605-613.
2. Lukes DJ, Herlenius G, Rizell M, et al. Late mortality in. 679 consecutive liver transplant recipients: the Gothenburg liver transplant experience. Transplant Proc, 2006, 38(8): 2671-2672.
3. Puig N, de la Rubia J, Remigia MJ, et al. Morbidity and transplant-related mortality of CBV and BEAM preparative regimens for patients with lymphoid malignancies undergoing autologous stem-cell transplantation. Leuk Lymphoma, 2006, 47(8): 1488-1494.
4. Sykes M. Immune tolerance: mechanisms and application in clinical transplantation. J Intern Med, 2007, 262(3): 288-310.
5. Xia G, Shah M, Luo X. Prevention of allograft rejection by amplification of Foxp3+CD4+CD25+ regulatory T cells. Transl Res, 2009, 153(2): 60-70.
6. Joffre O, Santolaria T, Calise D, et al. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat Med, 2008, 14(1): 88-92.
7. Meloni F, Vitulo P, Bianco AM, et al. Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: Correlation with transplant outcome. Transplantation, 2004, 77(5): 762-766.
8. Louis S, Braudeau C, Giral M, et al. Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. Transplantation, 2006, 81(3): 398-407.
9. Daniel V, Naujokat C, Sadeghi M, et al. Observational support for an immunoregulatory role of CD3+CD4+CD25+IFN-gamma+ blood lymphocytes in kidney transplant recipients with good long-term graft outcome. Transpl Int, 2008, 21(7): 646-660.
10. Akl A, Jones ND, Rogers N, et al. An investigation to assess the potential of CD25highCD4+ T cells to regulate responses to donor alloantigens in clinically stable renal transplant recipients. Transpl Int, 2008, 21(1): 65-73.
11. Jia LY, Yuan BB, Wang J, et al. Methods of Systematic Review of Health Policy Researches. Chin J Evid-Based Med, 2009, 9(10): 1037-1043.
12. Gregori S, Casorati M, Amuchastegui S, et al. Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol, 2001, 167(4): 1945-1953.
13. Chiffoleau E, Bériou G, Dutartre P, et al. Role for thymic and splenic regulatory CD4+ T cells induced by donor dendritic cells in allograft tolerance by LF15-0195 treatment. J Immunol, 2002, 168(10): 5058-5069.
14. Baan CC, van der Mast BJ, Klepper M, et al. Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation, 2005, 80(1): 110-117.
15. Demirkiran A, Kok A, Kwekkeboom J, et al. Decrease of CD4+CD25+ T cells in peripheral blood after liver transplantation: association with immunosuppression. Transplant Proc, 2005, 37(2): 1194-1196.
16. Tang W, Yang Y, Zhang F, et al. Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells. Int Immunopharmacol, 2005, 5(13-14): 1904-1913.
17. Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood, 2005, 105(12): 4743-4748.
18. Wang H, Zhao L, Sun Z, et al. A potential side effect of cyclosporin A: inhibition of CD4(+)CD25(+) regulatory T cells in mice. Transplantation, 2006, 82(11): 1484-1492.
19. Li W, Carper K, Liang Y, et al. Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance. Transplant Proc, 2006,38(10): 3207-3208.
20. San Segundo D, Ruiz JC, Fernández-Fresnedo G, et al. Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients. Transplant Proc, 2006, 38(8): 2391-2393.
21. Coenen JJ, Koenen HJ, van Rijssen E, et al. Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood, 2006, 107(3): 1018-1023.
22. Chavez H, Beaudreuil S, Abbed K, et al. Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade. Transpl Immunol, 2007, 17(4): 243-248.
23. Ardalan MR, Maljaei H, Shoja MM, et al. Calcitriol started in the donor, expands the population of CD4+CD25+ T cells in renal transplant recipients. Transplant Proc, 2007, 39(4): 951-953.
24. Lim DG, Joe IY, Park YH, et al. Effect of immunosuppressants on the expansion and function of naturally occurring regulatory T cells. Transpl Immunol, 2007, 18(2): 94-100.
25. Kreijveld E, Koenen HJ, Klasen IS, et al. Following anti-CD25 treatment, a functional CD4+CD25+ regulatory T-cell pool is present in renal transplant recipients. Am J Transplant, 2007, 7(1): 249-255.
26. Kopf H, de la Rosa GM, Howard OM, et al. Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int Immunopharmacol, 2007, 7(13): 1819-1824.
27. Coenen JJ, Koenen HJ, van Rijssen E, et al. Rapamycin, not cyclosporine, permits thymic generation and peripheral preservation of CD4+ CD25+ FoxP3+ T cells. Bone Marrow Transplant, 2007, 39(9): 537-545.
28. San Segundo D, Fábrega E, López-Hoyos M, et al. Reduced numbers of blood natural regulatory T cells in stable liver transplant recipients with high levels of calcineurin inhibitors. Transplant Proc, 2007, 39(7): 2290-2292.
29. Noris M, Casiraghi F, Todeschini M, et al. Regulatory T cells and T cell depletion: role of immunosuppressive drugs. J Am Soc Nephrol, 2007, 18(3): 1007-1018.
30. Ruggenenti P, Perico N, Gotti E, et al. Sirolimus versus cyclosporine therapy increases circulating regulatory T cells, but does not protect renal transplant patients given alemtuzumab induction from chronic allograft injury. Transplantation, 2007, 84(8): 956-964.
31. Qu Y, Zhang B, Zhao L, et al. The effect of immunosuppressive drug rapamycin on regulatory CD4+CD25+Foxp3+T cells in mice. Transpl Immunol, 2007, 17(3): 153-161.
32. Korczak-Kowalska G, Wierzbicki P, Bocian K, et al. The influence of immuosuppressive therapy on the development of CD4+CD25+ T cells after renal transplantation. Transplant Proc, 2007, 39(9): 2721-2723.
33. Kreijveld E, Koenen HJ, Hilbrands LB, et al. The immunosuppressive drug FK778 induces regulatory activity in stimulated human CD4+ CD25- T cells. Blood, 2007, 109(1): 244-252.
34. Morales J, Bono MR, Fierro A, et al. Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells. Transplant Proc, 2008, 40(9): 3223-3228.
35. Pascual J, Bloom D, Torrealba J, et al. Calcineurin inhibitor withdrawal after renal transplantation with alemtuzumab: clinical outcomes and effect on T-regulatory cells. Am J Transplant, 2008, 8(7): 1529-1536.
36. Bloom DD, Chang Z, Fechner JH, et al. CD4+ CD25+ FOXP3+ regulatory T cells increase de novo in kidney transplant patients after immunodepletion with Campath-1H. Am J Transplant, 2008, 8(4): 793-802.
37. Long SA, Buckner JH. Combination of rapamycin and IL-2 increases de novo induction of human CD4(+)CD25(+)FOXP3(+) T cells. J Autoimmun, 2008, 30(4): 293-302.
38. Liu Y, Chen Y, Liu FQ, et al. Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation. Transpl Int, 2008, 21(5): 483-494.
39. Yi H, Zhen Y, Zeng C, et al. Depleting anti-CD4 monoclonal antibody (GK1.5) treatment: influence on regulatory CD4+CD25+Foxp3+ T cells in mice. Transplantation, 2008, 85(8): 1167-1174.
40. Meng L, Wu Z, Wang Y, et al. Differential impact of CD154 costimulation blockade on alloreactive effector and regulatory T cells in murine renal transplant recipients. Transplantation, 2008, 85(9): 1332-1338.
41. Liu Z, Fang Y, Wang X, et al. Upregulation of molecules associated with T-regulatory function by thymoglobulin pretreatment of human CD4+ cells. Transplantation, 2008, 86(10): 1419-1426.
42. Bluestone JA, Liu W, Yabu JM, et al. The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am J Transplant, 2008, 8(10): 2086-2096.
43. Zeiser R, Leveson-Gower DB, Zambricki EA, et al. Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells. Blood, 2008, 111(1): 453-462.
44. Wang Z, Xiao L, Shi BY, et al. Short-term anti-CD25 monoclonal antibody treatment and neogenetic CD4(+)CD25(high) regulatory T cells in kidney transplantation. Transpl Immunol, 2008, 19(1): 69-73.
45. Hendrikx TK, Velthuis JH, Klepper M, et al. Monotherapy rapamycin allows an increase of CD4 CD25 FoxP3 T cells in renal recipients. Transpl Int, 2009, 22(9): 884-891.
46. Calvo-Turrubiartes M, Romano-Moreno S, García-Hernández M, et al. Quantitative analysis of regulatory T cells in kidney graft recipients: a relationship with calcineurin inhibitor level. Transpl Immunol, 2009, 21(1): 43-49.
47. Demirkiran A, Sewgobind VD, van der Weijde J, et al. Conversion from calcineurin inhibitor to mycophenolate mofetil-based immunosuppression changes the frequency and phenotype of CD4+FOXP3+ regulatory T cells. Transplantation, 2009, 87(7): 1062-1068.
48. Levitsky J, Miller J, Wang E, et al. Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents. Hum Immunol, 2009, 70(3): 146-150.
49. Singh AK, Horvath KA, Mohiuddin MM. Rapamycin promotes the enrichment of CD4(+)CD25(hi)FoxP3(+) T regulatory cells from na?ve CD4(+) T cells of baboon that suppress antiporcine xenogenic response in vitro. Transplant Proc, 2009, 41(1): 418-421.
50. Javeed A, Zhang B, Qu Y, et al. The significantly enhanced frequency of functional CD4+CD25+Foxp3+ T regulatory cells in therapeutic dose aspirin-treated mice. Transpl Immunol, 2009, 20(4): 253-260.

《中國循證醫學雜志》

移植排斥治療中不同免疫抑制劑對調節性T細胞活化及功能的影響：結合基礎和臨床的系統評價△

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《中國循證醫學雜志》

移植排斥治療中不同免疫抑制劑對調節性T細胞活化及功能的影響：結合基礎和臨床的系統評價△

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