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Вестник трансплантологии и искусственных органов

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ИНФОРМАЦИОННАЯ ЗНАЧИМОСТЬ МОНИТОРИНГА ПОПУЛЯЦИЙ СD4+ Т-ЛИМФОЦИТОВ В ДИАГНОСТИКЕ И ПРОГНОЗИРОВАНИИ РЕАКЦИИ ОРГАНИЗМА НА ТРАНСПЛАНТАТ

https://doi.org/10.15825/1995-1191-2013-4-112-125

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Аннотация

В обзоре обосновывается необходимость внедрения в клиническую практику комплексного мониторинга иммунных клеток крови и цитокинов у больных с пересаженными органами для выбора индивидуальной тактики иммуносупрессивной терапии, оценки ее эффективности и прогнозирования результатов. Подчеркивается, что с особым вниманием следует отнестись к характеристике CD4+ T-лимфоцитов и определению соотношения их отдельных популяций в периферической крови (Treg, Th17, Tact клетки памяти CD4+CD25hiCD127hiCD45RO), так как именно они являются основными участниками ответа иммунной системы организма на трансплантат. 

Об авторах

Н. А. Онищенко
Лаборатория клеточных технологий отдела биомедицинских технологий и тканевой инженерии (зав. – д. м. н., проф. Н.А. Онищенко) ФГБУ «ФНЦ трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздрава России (директор – академик РАМН, профессор С.В. Готье), Москва, Российская Федерация


Л. В. Башкина
Лаборатория клеточных технологий отдела биомедицинских технологий и тканевой инженерии (зав. – д. м. н., проф. Н.А. Онищенко) ФГБУ «ФНЦ трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздрава России (директор – академик РАМН, профессор С.В. Готье), Москва, Российская Федерация


А. О. Никольская
Лаборатория клеточных технологий отдела биомедицинских технологий и тканевой инженерии (зав. – д. м. н., проф. Н.А. Онищенко) ФГБУ «ФНЦ трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздрава России (директор – академик РАМН, профессор С.В. Готье), Москва, Российская Федерация


С. Д. Артамонов
Лаборатория клеточных технологий отдела биомедицинских технологий и тканевой инженерии (зав. – д. м. н., проф. Н.А. Онищенко) ФГБУ «ФНЦ трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздрава России (директор – академик РАМН, профессор С.В. Готье), Москва, Российская Федерация


Список литературы

1. СПИСОК ЛИТЕРАТУРЫ

2. Heidt S., Wood K.J. Biomarkers of operational tolerance in solid organ transplantation. Expert Opin Med Diagn. 2012 Jul; 6 (4): 281–293.

3. Lozano J.J., Pallier A., Martinez-Llordella M., Dan- ger R., López M., Giral M., Londoño M.C., Rimola A., Soulillou J.P., Brouard S., Sánchez-Fueyo A. Compari- son of transcriptional and blood cell-phenotypic markersbetween operationally tolerant liver and kidney recipi-

4. ents. Am. J. Transplant. 2011 Sep; 11 (9): 1916–1926.

5. Martínez-Llordella M., Puig-Pey I., Orlando G., Ramo- ni M., Tisone G., Rimola A., Lerut J., Latinne D., Mar- garit C., Bilbao I., Brouard S., Hernández-Fuentes M., Soulillou J.P., Sánchez-Fueyo A. Multiparameter immu- ne profiling of operational tolerance in liver transplanta-

6. tion. Am. J. Transplant. 2007 Feb; 7 (2): 309–319.

7. Mazariegos G.V., Reyes J., Marino I.R., Demetris A.J., Flynn B., Irish W., McMichael J., Fung J.J., Starzl T.E. Weaning of immunosuppression in liver transplant reci-

8. pients. Transplantation. 1997 Jan 27; 63 (2): 243–249.

9. Pons J.A., Revilla-Nuin B., Baroja-Mazo A., Ramírez P., Martínez-Alarcón L., Sánchez-Bueno F., Robles R., Rios A., Aparicio P., Parrilla P. FoxP3 in peripheral blood is associated with operational tolerance in liver transplant patients during immunosuppression with- drawal. Transplantation. 2008 Nov 27; 86 (10): 1370–

10.

11. Orlando G., Manzia T., Baiocchi L., Sanchez-Fueyo A.,

12. Angelico M., Tisone G. The Tor Vergata weaning off im- munosuppression protocol in stable HCV liver transplant patients: the updated follow up at 78 months. Transpl. Immunol. 2008 Nov; 20 (1–2): 43–47.

13. Eason J.D., Cohen A.J., Nair S., Alcantera T., Loss G.E. Tolerance: is it worth the risk? Transplantation. 2005 May 15; 79 (9): 1157–1159.

14. Girlanda R., Rela M., Williams R., O'Grady J.G., Hea- ton N.D. Long-term outcome of immunosuppression withdrawal after liver transplantation. Transplant Proc. 2005 May; 37 (4): 1708–1711.

15. Онищенко Н.А., Артамонов С.Д., Крашенинников М.Е., Башкина Л.В., Никольская А.О. Индивидуальная ус- тойчивость стереотипов иммунного реагирования и современные возможности их диагностики при транс- плантации органов (иммуно-физиологический анализ проблемы). Вестник трансплантологии и иск. орга- нов. 2013; 15 (2): 123–134.

16. Feng S., Ekong U.D., Lobritto S.J., Demetris A.J., Roberts J.P., Rosenthal P., Alonso E.M., Philoge- ne M.C., Ikle D., Poole K.M., Bridges N.D., Turka L.A., Tchao N.K. Complete immunosuppression withdrawal and subsequent allograft function among pediatric reci- pients of parental living donor liver transplants. JAMA. 2012 Jan 18; 307 (3): 283–293.

17. Demetris A.J., Lunz J.G. 3rd, Randhawa P., Wu T., Na- lesnik M., Thomson A.W. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology per- spective. Transpl. Int. 2009 Jan; 22 (1): 120–141.

18. Devlin J., Doherty D., Thomson L., Wong T., Donald- son P., Portmann B. Defining the outcome of immuno- suppression withdrawal after liver transplantation. He- patology. 1998; 27: 926–933.

19. Wong T., Nouri-Aria K.T., Devlin J., Portmann B., Wil- liams R. Tolerance and latent cellular rejection in long- term liver transplant recipients. Hepatology. 1998 Aug; 28 (2): 443–449.

20. Bingaman A.W., Farber D.L. Memory T cells in trans- plantation: generation, function, and potential role in re- jection. Am. J. Transplant. 2004 Jun; 4 (6): 846–852.

21. Welsh R.M., Selin L.K. No one is naive: the significance of heterologous T-cell immunity. Nat. Rev. Immunol. 2002 Jun; 2 (6): 417–426.

22. Strom T.B., Koulmanda M.J. Recently discovered T cell subsets cannot keep their commitments. Am. Soc. Neph- rol. 2009 Aug; 20 (8): 1677–1680.

23. Keever-Taylor C.A., Browning M.B., Johnson B.D., Truitt R.L., Bredeson C.N., Behn B., Tsao A. Rapamy- cin enriches for CD4(+) CD25(+) CD27(+) Foxp3(+) regulatory T cells in ex vivo-expanded CD25-enriched products from healthy donors and patients with multiple sclerosis. Cytotherapy. 2007; 9 (2): 144–157.

24. Coenen J.J., Koenen H.J., van Rijssen E., Hilbrands L.B., Joosten I. Rapamycin, and not cyclosporin A, preser- ves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood. 2006 Feb 1; 107 (3): 1018–1023.

25. Chadha R., Heidt S., Jones N.D., Wood K.J. Th17: con- tributors to allograft rejection and a barrier to the induc- tion of transplantation tolerance? Transplantation. 2011 May 15; 91 (9): 939–945.

26. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Pillars article: immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tole- rance causes various autoimmune diseases. J. Immunol. 2011 Apr 1; 186 (7): 3808–3821.

27. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Sci- ence. 2003 Feb 14; 299 (5609): 1057–1061.

28. Muller Y.D., Seebach J.D., Bühler L.H., Pascual M., Gols- hayan D. Transplantation tolerance: Clinical potential of regulatory T cells. Self Nonself. 2011 Jan; 2 (1): 26–34.

29. Baecher-Allan C., Wolf E., Hafler D.A. Functional ana- lysis of highly defined, FACS-isolated populations of human regulatory CD4+ CD25+ T cells. Clin. Immunol. 2005 Apr; 115 (1): 10–18.

30. Liu W., Putnam A.L., Xu-Yu Z., Szot G.L., Lee M.R., Zhu S., Gottlieb P.A., Kapranov P., Gingeras T.R., Fa- zekas de St Groth B., Clayberger C., Soper D.M., Zieg- ler S.F., Bluestone J.A. CD127 expression inversely cor- relates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 2006 Jul 10; 203 (7): 1701–1711.

31. Seddiki N., Santner-Nanan B., Martinson J., Zaunders J., Sasson S., Landay A., Solomon M., Selby W., Alexan- der S.I., Nanan R., Kelleher A., Fazekas de St Groth B. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 2006 Jul 10; 203 (7): 1693–1700.

32. Sánchez-Fueyo A., Strom T.B. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology. 2011 Jan; 140 (1): 51–64.

33. Codarri L., Vallotton L., Ciuffreda D., Venetz J.P., Gar- cia M., Hadaya K., Buhler L., Rotman S., Pascual M., Pantaleo G. Expansion and tissue infiltration of an allo- specific CD4+CD25+CD45RO+IL-7Ralphahigh cell population in solid organ transplant recipients. J. Exp. Med. 2007 Jul 9; 204 (7): 1533–1541.

34. Vallotton L., Hadaya K., Venetz J.P., Buehler L.H., Ciuf- freda D., Nseir G., Codarri L., Villard J., Pantaleo G., Pascual M. Monitoring of CD4+CD25highIL-7Rαhigh activated T cells in kidney transplant recipients. Clin. J. Am. Soc. Nephrol. 2011 Aug; 6 (8): 2025–2033.

35. Schmidt-Lucke C., Aicher A., Romagnani P., Gareis B., Romagnani S., Zeiher A.M., Dimmeler S. Specific rec- ruitment of CD4+CD25++ regulatory T cells into the allograft in heart transplant recipients. Am. J. Physiol. Heart. Circ. Physiol. 2007 May; 292 (5): H2425–31.

36. Chen J.F., Gao J., Zhang D., Wang Z.H., Zhu J.Y. CD4+Foxp3+ regulatory T cells converted by rapamy- cin from peripheral CD4+CD25(-) naive T cells display more potent regulatory ability in vitro. Chin. Med. J. (Engl). 2010 Apr 5; 123 (7): 924–928.

37. Mosmann T.R., Cherwinski H., Bond M.W., Giedlin M.A., Coffman R.L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 1986 Apr 1; 136 (7): 2348–2357.

38. Burrell B.E., Bishop D.K. Th17 cells and transplant ac- ceptance. Transplantation. 2010 Nov 15; 90 (9): 945– 948.

39. Afzali B., Lombardi G., Lechler R.I., Lord G.M. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin. Exp. Immunol. 2007 Apr; 148 (1): 32–46.

40. Reiner S.L. Development in motion: helper T cells at work. Cell. 2007 Apr 6; 129 (1): 33–36.

41. Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat. Rev. Immunol. 2008 May; 8 (5): 337–348.

42. Wahl S.M. Mangan P.R., Harrington L.E., O'Quinn D.B., Helms W.S., Bullard D.C., Elson C.O., Hatton R.D., Schoeb T.R., Weaver C.T. Transforming growth factor- beta induces development of the T(H)17 lineage. Nature. 2006 May 11; 441 (7090): 231–234.

43. Puel A., Döffinger R., Natividad A., Chrabieh M., Barcenas-Morales G., Picard C., Cobat A., Ouachée- Chardin M., Toulon A., Bustamante J., Al-Muhsen S., Al-Owain M., Arkwright P.D., Costigan C., McCon- nell V., Cant A.J., Abinun M., Polak M., Bougnères P.F., Kumararatne D., Marodi L., Nahum A., Roifman C., Blanche S., Fischer A., Bodemer C., Abel L., Lilic D., Casanova J.L. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candi- diasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 2010 Feb 15; 207 (2): 291–297.

44. Ji Y., Zhang W. Th17 cells: positive or negative role in tumor? Cancer Immunol. Immunother. 2010 Jul; 59 (7): 979–987.

45. Acosta-Rodriguez E.V., Rivino L., Geginat J., Jarros- say D., Gattorno M., Lanzavecchia A., Sallusto F., Napo- litani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat. Immunol. 2007 Jun; 8 (6): 639–646.

46. Shah K., Lee W.W., Lee S.H., Kim S.H., Kang S.W., Craft J., Kang I. Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus. Arthritis. Res. Ther. 2010; 12 (2): R53.

47. Heidt S., Segundo D.S., Chadha R., Wood K.J. The im- pact of Th17 cells on transplant rejection and the induc- tion of tolerance. Curr. Opin Organ Transplant. 2010 Aug; 15 (4): 456–461.

48. Abadja F., Sarraj B., Ansari M.J. Significance of T hel- per 17 immunity in transplantation. Curr. Opin Organ Transplant. 2012 Feb; 17 (1): 8–14.

49. Miura M., El-Sawy T., Fairchild R.L. Neutrophils mediate parenchymal tissue necrosis and accelerate the rejection of complete major histocompatibility complex-disparate cardiac allografts in the absence of interferon-gamma. Am. J. Pathol. 2003 Feb; 162 (2): 509–519.

50. Yu X., Jiang Y., Lu L., Gong X., Sun X., Xuan Z. A cru- cial role of IL-17 and IFN-γ during acute rejection of peripheral nerve xenotransplantation in mice. PLoS One. 2012; 7 (3): e34419.

51. Li T., Si Z., Qi H., He Z., Li Y. IL-17 in the early diagnosis of acute renal allograft rejection in mice. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Dec; 36 (12): 1147–1152.

52. Itoh S., Kimura N., Axtell R.C., Velotta J.B., Gong Y., Wang X., Kajiwara N., Nambu A., Shimura E., Adachi H., Iwakura Y., Saito H., Okumura K., Sudo K., Steinman L., Robbins R.C., Nakae S., Fischbein M.P. Interleukin-17 accelerates allograft rejection by suppressing regulato- ry T cell expansion. Circulation. 2011 Sep 13; 124 (11): S187–196.

53. Yuan X., Paez-Cortez J., Schmitt-Knosalla I., D'Addio F., Mfarrej B., Donnarumma M., Habicht A., Clarkson M.R., Iacomini J., Glimcher L.H., Sayegh M.H., Ansari M.J. A novel role of CD4 Th17 cells in mediating cardiac allo- graft rejection and vasculopathy. J. Exp. Med. 2008 Dec 22; 205 (13): 3133–3144.

54. Xie X., Ye Y., Zhou L., Xie H., Jiang G., Feng X., He Y., Xie Q., Zheng S. Th17 promotes acute rejection following liver transplantation in rats. j Zhejiang Univ-Sci B. Bio- med & Biotechnol. 2010; 11 (11): 819–827.

55. Fábrega E., López-Hoyos M., San Segundo D., Casa- font F., Pons-Romero F. Changes in the serum levels of interleukin-17/interleukin-23 during acute rejection in liver transplantation. Liver Transpl. 2009 Jun; 15 (6): 629–633.

56. Vanaudenaerde B.M., De Vleeschauwer S.I., Vos R., Meyts I., Bullens D.M., Reynders V., Wuyts W.A., Van Ra- emdonck D.E., Dupont L.J., Verleden G.M. The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation. Am. J. Transplant. 2008 Sep; 8 (9): 1911–1920.

57. Chung B.H., Oh H.J., Piao S.G., Sun I.O., Kang S.H., Choi S.R., Park H.S., Choi B.S., Choi Y.J., Park C.W., Kim Y.S., Cho M.L., Yang C.W. Higher infiltration by Th17 cells compared with regulatory T cells is associ- ated with severe acute T-cell-mediated graft rejection. Exp. Mol Med. 2011 Nov 30; 43 (11): 630–637.

58. Awasthi A., Murugaiyan G., Kuchroo V.K. Interplay bet- ween effector Th17 and regulatory T cells. J. Clin. Im- munol. 2008 Nov; 28 (6): 660–670.

59. Fan H., Li L.X., Han D.D., Kou J.T., Li P., He Q. Incre- ase of peripheral Th17 lymphocytes during acute cellu- lar rejection in liver transplant recipients. Hepatobiliary Pancreat. Dis. Int. 2012 Dec 15; 11 (6): 606–611.

60. Chung B.H., Kim K.W., Kim B.M., Piao S.G., Lim S.W., Choi B.S., Park C.W., Kim Y.S., Cho M.L., Yang C.W. Dysregulation of Th17 cells during the early post-trans- plant period in patients under calcineurin inhibitor based immunosuppression. PLoS One. 2012; 7 (7): e42011.

61. Syrjälä S.O., Keränen M.A., Tuuminen R., Nykänen A.I., Tammi M., Krebs R., Lemström K.B. Increased Th17 rather than Th1 alloimmune response is associated with cardiac allograft vasculopathy after hypothermic preser- vation in the rat. J. Heart. Lung Transplant. 2010 Sep; 29 (9): 1047–1057.

62. Liu Z., Yuan X., Luo Y., He Y., Jiang Y., Chen Z.K., Sun E. Evaluating the effects of immunosuppressants on human immunity using cytokine profiles of whole blood. Cyto- kine. 2009 Feb; 45 (2): 141–147.

63. Abadja F., Videcoq C., Alamartine E., Berthoux F., Mari- at C. Differential effect of cyclosporine and mycopheno- lic acid on the human regulatory T cells and TH-17 cells balance. Transplant. Proc. 2009 Oct; 41 (8): 3367–3370.

64. Zhang C., Zhang J., Yang B., Wu C. Cyclosporin A inhi- bits the production of IL-17 by memory Th17 cells from healthy individuals and patients with rheumatoid arthri- tis. Cytokine. 2008 Jun; 42 (3): 345–352.

65. Haider A.S., Lowes M.A., Suárez-Fariñas M., Zaba L.C., Cardinale I., Khatcherian A., Novitskaya I., Wittkows- ki K.M., Krueger J.G. Identification of cellular pathways of «type 1», Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyc- losporine A in psoriasis. J. Immunol. 2008 Feb 1; 180 (3):1913–1920.

66. Abadja F., Atemkeng S., Alamartine E., Berthoux F., Ma- riat C. Impact of mycophenolic acid and tacrolimus on Th17-related immune response. Transplantation. 2011 Aug 27; 92 (4): 396–403.

67. Kopf H., de la Rosa G.M., Howard O.M., Chen X. Rapa- mycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+ T regulatory cells. Int. Immuno- pharmacol. 2007 Dec 15; 7 (13): 1819–1824.

68. Annunziato F., Cosmi L., Santarlasci V., Maggi L., Liotta F., Mazzinghi B., Parente E., Filì L., Ferri S., Frosali F., Giu- dici F., Romagnani P., Parronchi P., Tonelli F., Maggi E., Romagnani S. Phenotypic and functional features of human Th17 cells. J. Exp. Med. 2007 Aug 6; 204 (8): 1849–1861.

69. Stummvoll G.H., DiPaolo R.J., Huter E.N., David- son T.S., Glass D., Ward J.M., Shevach E.M. Th1, Th2, and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J. Immunol. 2008 Aug 1; 181 (3): 1908–1916.

70. Benghiat F.S., Craciun L., De Wilde V., Dernies T., Kub- jak C., Lhomme F., Goldman M., Le Moine A. IL-17 pro- duction elicited by allo-major histocompatibility com- plex class II recognition depends on CD25posCD4pos T cells. Transplantation. 2008 Apr 15; 85 (7): 943–949.

71. Van Y.H., Lee W.H., Ortiz S., Lee M.H., Qin H.J., Liu C.P. All-trans retinoic acid inhibits type 1 diabetes by T re- gulatory (Treg)-dependent suppression of interferon- gamma-producing T-cells without affecting Th17 cells. Diabetes. 2009 Jan; 58 (1): 146–155.

72. Braun R.K., Molitor-Dart M., Wigfield C., Xiang Z., Fain S.B., Jankowska-Gan E., Seroogy C.M., Bur- lingham W.J., Wilkes D.S., Brand D.D., Torrealba J., Love R.B. Transfer of tolerance to collagen type V sup- presses T-helper-cell-17 lymphocyte-mediated acute lung transplant rejection. Transplantation. 2009 Dec 27; 88 (12): 1341–1348.

73. Huter E.N., Stummvoll G.H., DiPaolo R.J., Glass D.D., Shevach E.M. Cutting edge: antigen-specific TGF beta- induced regulatory T cells suppress Th17-mediated au- toimmune disease. J. Immunol. 2008 Dec 15; 181 (12): 8209–8213.

74. Zhou L., Lopes J.E., Chong M.M., Ivanov I.I., Min R., Victora G.D., Shen Y., Du J., Rubtsov Y.P., Ruden- sky A.Y., Ziegler S.F., Littman D.R. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagoni- zing RORgammat function. Nature. 2008 May 8; 453 (7192): 236–240.

75. Afzali B., Mitchell P., Lechler R.I., John S., Lombardi G. Translational mini-review series on Th17 cells: induc- tion of interleukin-17 production by regulatory T cells. Clin. Exp. Immunol. 2010 Feb; 159 (2): 120–130.

76. Lundgren A., Strömberg E., Sjöling A., Lindholm C., Enarsson K., Edebo A., Johnsson E., Suri-Payer E., Larsson P., Rudin A., Svennerholm A.M., Lundin B.S. Mucosal FOXP3-expressing CD4+ CD25high regulato- ry T cells in Helicobacter pylori-infected patients. Infect. Immun. 2005 Jan; 73 (1): 523–531.

77. Vokaer B., Van Rompaey N., Lemaître P.H., Lhommé F., Kubjak C., Benghiat F.S., Iwakura Y., Petein M., Field K.A., Goldman M., Le Moine A., Charbonnier L.M. Critical role of regulatory T cells in Th17-mediated mi- nor antigen-disparate rejection. J. Immunol. 2010 Sep 15; 185 (6): 3417–3425.


Для цитирования:


Онищенко Н.А., Башкина Л.В., Никольская А.О., Артамонов С.Д. ИНФОРМАЦИОННАЯ ЗНАЧИМОСТЬ МОНИТОРИНГА ПОПУЛЯЦИЙ СD4+ Т-ЛИМФОЦИТОВ В ДИАГНОСТИКЕ И ПРОГНОЗИРОВАНИИ РЕАКЦИИ ОРГАНИЗМА НА ТРАНСПЛАНТАТ. Вестник трансплантологии и искусственных органов. 2013;15(4):112-125. https://doi.org/10.15825/1995-1191-2013-4-112-125

For citation:


Onishchenko N.A., Bashkina L.V., Nicolskaya A.O., Artamonov S.D. SIGNIFICANCE OF СD4+ Т-LYMPHOCYTE POPULATIONS MONITORING FOR DIAGNOSING AND FORECASTING OF ORGANISM REACTION ON TRANSPLANT. Russian Journal of Transplantology and Artificial Organs. 2013;15(4):112-125. (In Russ.) https://doi.org/10.15825/1995-1191-2013-4-112-125

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