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ИММУНОБИОЛОГИЯ ОСТРОЙ РЕАКЦИИ «ТРАНСПЛАНТАТ ПРОТИВ ХОЗЯИНА»

https://doi.org/10.15789/1563-0625-2015-6-499-516

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Аннотация

Для целого ряда заболеваний системы кроветворения единственным методом излечения является аллогенная трансплантация гемопоэтических стволовых клеток, которая имеет своей целью замену кроветворной системы реципиента на донорскую. Однако попадание в организм реципиента содержащихся в трансплантате зрелых Т-лимфоцитов может приводить к развитию тяжелого пост-трансплантационного осложнения – реакции «трансплантат против хозяина» (РТПХ). Она вызвана тем, что иммунная система донора содержит клоны Т-лимфоцитов, специфичные к аллоантигенам реципиента, которые, встречая свои антигены, активируются и вызывают системное повреждение здоровых тканей. Наличие аллореактивных клонов обусловлено генетическими различиями между донором и реципиентом. Важнейшим фактором, определяющим успех трансплантации, является совместимость по генам главного комплекса гистосовместимости, которые экспрессируются во всех ядерных клетках и отвечают за презентацию антигенов клеткам иммунной системы. В настоящее время созданы обширные банки доноров стволовых гемопоэтических клеток, которые позволяют подобрать для большинства пациентов совместимого донора. Однако это не полностью предотвращает развитие РПТХ, так как помимо генов главного комплекса гистосовместимости, донор и реципиент могут различаться по так называемым минорным антигенам совместимости. Минорные антигены обусловлены генетическими полиморфизмами во всех кодирующих областях генома. Дополнительным фактором, способствующим развитию реакции «трансплантат против хозяина», является предтрансплантационная подготовка пациента, которая необходима для приживления трансплантата, но в качестве побочного эффекта приводит к формированию в организме реципиента провоспалительного окружения. Тяжелые формы РТПХ развиваются приблизительно у 40% пациентов, совпадающих по генам главного комплекса гистосовместимости, а в случаях неполной совместимости эта доля еще больше. Смертность от РТПХ сравнима с другими причинами посттрансплантационной летальности, такими как рецидив изначального заболевания и вирусные инфекции. Таким образом, развитие тяжелых форм РТПХ существенно лимитирует клиническое применение трансплантации стволовых кроветворных клеток. Агрессивная иммуносупрессия или исключение из трансплантата донора зрелых Т-лимфоцитов приводит к увеличению вероятности рецидива и ослабляет противоинфекционный иммунитет, что требует поиска альтернативных, более специфичных путей профилактики реакции «трансплантат против хозяина». В настоящем обзоре будут рассмотрены механизмы формирования аллореактивных клонов Т-лимфоцитов и этапы патогенеза острой формы реакции «трансплантат против хозяина».

Об авторах

Г. А. Ефимов
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

к.б.н., заведующий лабораторией трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия 125167, Россия, Москва, Новый Зыковский пр., 4. Тел.: 8 (964) 551-55-51



А. С. Вдовин
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



А. А. Григорьев
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

к.б.н, научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



С. Ю. Филькин
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



Н. А. Быкова
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



В. Г. Савченко
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

д.м.н., профессор, академик РАН, генеральный директор ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



Список литературы

1. Боголюбова А.В., Ефимов Г.А., Друцкая М.С., Недоспасов С.А. Иммунотерапия опухолей, основанная на блокировке иммунологических контрольных «точек» («чекпойнтов») // Медицинская иммунология, 2015, Т. 17, № 5. С. 395-406. [Bogolyubova A.V., Efimov G.A., Drutskaya M.S., Nedospasov S.A. Cancer immunotherapy based on the blockade of immune checkpoints. Meditsinskaya Immunologiya = Medical Immunology (Russia), 2015, Vol. 17, no. 5, pp. 395-406. doi: 10.15789/1563-0625-2015-5-395-406 (In Russ.)]

2. Alexandrov L.B., Nik-Zainal S., Wedge D.C., Aparicio S.A., Behjati S., Biankin A.V., Bignell G.R., Bolli N., Borg A., Borresen-Dale A.L., Boyault S., Burkhardt B., Butler A.P., Caldas C., Davies H.R., Desmedt C., Eils R., Eyfjord J.E., Foekens J.A., Greaves M., Hosoda F., Hutter B., Ilicic T., Imbeaud S., Imielinski M., Jager N., Jones D.T., Jones D., Knappskog S., Kool M., Lakhani S.R., Lopez-Otin C., Martin S., Munshi N.C., Nakamura H., Northcott P.A., Pajic M., Papaemmanuil E., Paradiso A., Pearson J.V., Puente X.S., Raine K., Ramakrishna M., Richardson A.L., Richter J., Rosenstiel P., Schlesner M., Schumacher T.N., Span P.N., Teague J.W., Totoki Y., Tutt A.N., Valdes-Mas R., van Buuren M.M., van ‘t Veer L., Vincent-Salomon A., Waddell N., Yates L.R., Australian I. Pancreatic Cancer Genome, I.B.C. Consortium, I. M.-S. Consortium, PedBrain I., Zucman-Rossi J., Futreal P.A., McDermott U., Lichter P., Meyerson M., Grimmond S.M., Siebert R., Campo E., Shibata T., Pfister S.M., Campbell P.J., Stratton M.R. Signatures of mutational processes in human cancer. Nature, 2013, Vol. 500, pp. 415-421.

3. Alyea E.P., Kim H.T., Ho V., Cutler C., DeAngelo D.J., Stone R., Ritz J., Antin J.H., Soiffer R.J. Impact of conditioning regimen intensity on o utcome of allogeneic hematopoietic cell transplantation for advanced acute myelogenous leukemia and myelodysplastic syndrome. Biol. Blood Marrow Transplant., 2006, Vol. 12, pp. 1047-1055.

4. Anasetti C., Beatty P.G., Storb R., Martin P.J., Mori M., Sanders J.E., Thomas E.D., Hansen J.A. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum. Immunol., 1990, Vol. 29, pp. 79-91.

5. Anderson B.E., McNiff J., Yan J., Doyle H., Mamula M., Shlomchik M.J., Shlomchik W.D. Memory CD4+ T cells do not induce graft-versus-host disease. J. Clin. Invest., 2003, Vol. 112, pp. 101-108.

6. Anderson B.E., Taylor P.A., McNiff J.M., Jain D., Demetris A.J., Panoskaltsis-Mortari A., Ager A., Blazar B.R., Shlomchik W.D., Shlomchik M.J. Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood, 2008, Vol. 111, pp. 5242-5251.

7. Antin J.H., Weisdorf D., Neuberg D., Nicklow R., Clouthier S., Lee S.J., Alyea E., McGarigle C., Blazar B.R., Sonis S., Soiffer R.J., Ferrara J.L. Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood, 2002, Vol. 100, pp. 3479-3482.

8. Atkins R.C., Ford W.L. Early cellular events in a systemic graft-vs.-host reaction. I. The migration of responding and nonresponding donor lymphocytes. J. Exp. Med., 1975, Vol. 141, pp. 664-680.

9. Bassani-Sternberg M., Pletscher-Frankild S., Jensen L.J., Mann M.Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation. Mol. Cell Proteomics, 2015, Vol. 14, pp. 658-673.

10. Baxter A.G., Hodgkin P.D. Activation rules: the two-signal theories of immune activation. Nat. Rev. Immunol., 2002, Vol. 2, pp. 439-446.

11. Beelen D.W., Elmaagacli A., Muller K.D., Hirche H., Schaefer U.W. Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graftversus-host disease after marrow transplantation in patients with hematologic malignancies: final results and longterm follow-up of an open-label prospective randomized trial. Blood, 1999, Vol. 93, pp. 3267-3275.

12. Bjorkman P.J., Saper M.A, Samraoui B., Bennett W.S., Strominger J.L., Wiley D.C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature, 1987, Vol. 329, pp. 506-512.

13. Blazar B.R., Murphy W.J., Abedi M. Advances in graft-versus-host disease biology and therapy. Nat. Rev. Immunol., 2012, Vol. 12, pp. 443-458.

14. Blazar B.R., Taylor P.A., Vallera D.A. CD4+ and CD8+ T cells each can utilize a perforin-dependent pathway to mediate lethal graft-versus-host disease in major histocompatibility complex-disparate recipients. Transplantation, 1997, Vol. 64, pp. 571-576.

15. Bleakley M., Heimfeld S., Jones L.A., Turtle C., Krause D., Riddell S.R., Shlomchik W. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol. Blood Marrow Transplant., 2014, Vol. 20, pp. 705-716.

16. Bleakley M., Otterud B.E., Richardt J.L., Mollerup A.D., Hudecek M., Nishida T., Chaney C.N., Warren E.H., Leppert M.F., Riddell S.R. Leukemia-associated minor histocompatibility antigen discovery using T-cell clones isolated by in vitro stimulation of naive CD8+ T cells. Blood, 2010, Vol. 115, pp. 4923-4933.

17. Bleakley M., Riddell S.R. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat. Rev. Cancer, 2004, Vol. 4, pp. 371-380.

18. Bouazzaoui A., Spacenko E., Mueller G., Huber E., Schubert T., Holler E., Andreesen R., Hildebrandt G.C. Steroid treatment alters adhesion molecule and chemokine expression in experimental acute graft-vs.-host disease of the intestinal tract. Exp. Hematol., 2011, Vol. 39, pp. 238-249 e231.

19. Brunstein C.G., Miller J.S., Cao Q., McKenna D.H., Hippen K.L., Curtsinger J., Defor T., Levine B.L., June C.H., Rubinstein P., McGlave P.B., Blazar B.R., Wagner J.E. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood, 2011, Vol. 117, pp. 1061-1070.

20. Burman A.C., Banovic T., Kuns R.D., Clouston A.D., Stanley A.C., Morris E.S., Rowe V., Bofinger H., Skoczylas R., Raffelt N., Fahy O., McColl S.R., Engwerda C.R., McDonald K.P., Hill G.R. IFNgamma differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract. Blood, 2007, Vol. 110, pp. 1064-1072.

21. Cavazzana-Calvo M., Carlier F., Le Deist F., Morillon E., Taupin P., Gautier D., Radford-Weiss I., Caillat-Zucman S., Neven B., Blanche S., Cheynier R., Fischer A., Hacein-Bey-Abina S. Long-term T-cell reconstitution after hematopoietic stem-cell transplantation in primary T-cell-immunodeficient patients is associated with myeloid chimerism and possibly the primary disease phenotype. Blood, 2007, Vol. 109, pp. 4575-4581.

22. Cavet J., Dickinson A.M., Norden J., Taylor P.R., Jackson G.H., Middleton P.G. Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus-host disease in HLA-matched sibling bone marrow transplantation. Blood, 2001, Vol. 98, pp. 1594-1600.

23. Cavet J., Middleton P.G., Segall M., Noreen H., Davies S.M., Dickinson A.M. Recipient tumor necrosis factor-alpha and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants. Blood, 1999, Vol. 94, pp. 3941-3946.

24. Chakraverty R., Cote D., Buchli J., Cotter P., Hsu R., Zhao G., Sachs T., Pitsillides C.M., Bronson R., Means T., Lin C., Sykes M. An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. J. Exp. Med., 2006, Vol. 203, pp. 2021-2031.

25. Champlin R., Khouri I., Shimoni A., Gajewski J., Kornblau S., Molldrem J., Ueno N., Giralt S., Anderlini P. Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. Br. J. Haematol., 2000, Vol. 111, pp. 18-29.

26. Chen Y., Zhao Y., Cheng Q., Wu D., Liu H. The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease. J. Immunol. Res., 2015, Vol. 2015, p. 145859.

27. Choi S.W., Reddy P. Current and emerging strategies for the prevention of graft-versus-host disease. Nat. Rev. Clin. Oncol., 2014, Vol. 11, pp. 536-547.

28. Choo S.Y. The HLA system: genetics, immunology, clinical testing, and clinical implications. Yonsei Med. J., 2007, Vol. 48, pp. 11-23.

29. Chung W.H., Hung S.I., Hong H.S., Hsih M.S., Yang L.C., Ho H.C., Wu J.Y., Chen Y.T. Medical genetics: a marker for Stevens-Johnson syndrome. Nature, 2004, Vol. 428, p. 486.

30. Cooke K.R. Acute lung injury after allogeneic stem cell transplantation: from the clinic, to the bench and back again. Pediatr. Transplant., 2005, Vol. 9, Suppl. 7, pp. 25-36.

31. Crocchiolo R., Zino E., Vago L., Oneto R., Bruno B., Pollichieni S., Sacchi N., Sormani M.P., Marcon J., Lamparelli T., Fanin R., Garbarino L., Miotti V., Bandini G., Bosi A., Ciceri F., Bacigalupo A., Fleischhauer K., T.C. Gruppo Italiano Trapianto di Midollo Osseo and R. Italian Bone Marrow Donor. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation. Blood,

32. , Vol. 114, pp. 1437-1444.

33. Cullup H., Dickinson A.M., Jackson G.H., Taylor P.R., Cavet J., Middleton P.G. Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants. Br. J. Haematol., 2001, Vol. 113, pp. 807-813.

34. Cullup H., Stark G. Interleukin-1 polymorphisms and graft-vs-host disease. Leuk. Lymphoma, 2005, Vol. 46, pp. 517-523.

35. D’Orsogna L.J., Nguyen T.H, Claas F.H., Witt C., Mifsud N.A. Endogenous-peptide-dependent alloreactivity: new scientific insights and clinical implications. Tissue Antigens, 2013, Vol. 81, pp. 399-407.

36. Danke N.A., Koelle D.M., Yee C., Beheray S., Kwok W.W. Autoreactive T cells in healthy individuals. J. Immunol., 2004, Vol. 172, pp. 5967-5972.

37. Dutcher J. Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma. Oncology (Williston Park), 2002, Vol. 16, pp. 4-10.

38. Dutt S., Ermann J., Tseng D., Liu Y.P., George T.I., Fathman C.G., Strober S. L-selectin and beta7 integrin on donor CD4 T cells are required for the early migration to host mesenteric lymph nodes and acute colitis of graftversus-host disease. Blood, 2005, Vol. 106, pp. 4009-4015.

39. Dzierzak-Mietla M., Markiewicz M., Siekiera U., Mizia S., Koclega A., Zielinska P., Sobczyk-Kruszelnicka M., Kyrcz-Krzemien S. Occurrence and Impact of Minor Histocompatibility Antigens’ Disparities on Outcomes of Hematopoietic Stem Cell Transplantation from HLA-Matched Sibling Donors. Bone Marrow Res., 2012, Vol. 2012, p. 257086.

40. Eyrich M., Burger G., Marquardt K., Budach W., Schilbach K., Niethammer D., Schlegel P.G. Sequential expression of adhesion and costimulatory molecules in graft-versus-host disease target organs after murine bone marrow transplantation across minor histocompatibility antigen barriers. Biol. Blood Marrow Transplant., 2005, Vol. 11, pp. 371-382.

41. Ferrara J.L., Deeg H.J. Graft-versus-host disease. N. Engl. J. Med., 1991, Vol. 324, pp. 667-674.

42. Ferrara J.L., Levy R., Chao N.J. Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol. Blood Marrow Transplant., 1999, Vol. 5, pp. 347-356.

43. Fleischhauer K., Kernan N.A., O’Reilly R.J., Dupont B., Yang S.Y. Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44. N. Engl. J. Med., 1990, Vol. 323, pp. 1818-1822.

44. Funke V.A., de Medeiros C.R., Setubal D.C., Ruiz J., Bitencourt M.A., Bonfim C.M., Neto J.Z., Pasquini R. Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist. Bone Marrow Transplant., 2006, Vol. 37, pp. 961-965.

45. Gale R.P., Horowitz M.M., Ash R.C., Champlin R.E., Goldman J.M., Rimm A.A., Ringden O., Stone J.A., Bortin M.M. Identical-twin bone marrow transplants for leukemia. Ann. Intern. Med., 1994, Vol. 120, pp. 646-652.

46. Garcia K.C., Degano M., Stanfield R.L., Brunmark A., Jackson M.R., Peterson P.A., Teyton L., Wilson I.A. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex. Science, 1996, Vol. 274, pp. 209-219.

47. Gerbitz A., Schultz M., Wilke A., Linde H.J., Scholmerich J., Andreesen R., Holler E. Probiotic effects on experimental graft-versus-host disease: let them eat yogurt. Blood, 2004, Vol. 103, pp. 4365-4367.

48. Gerhardt T., Ley K. Monocyte trafficking across the vessel wall. Cardiovasc. Res., 2015, Vol. 107, pp. 321-330.

49. Glucksberg H., Storb R., Fefer A., Buckner C.D., Neiman P.E., Clift R.A., Lerner K.G., Thomas E.D. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation, 1974, Vol. 18, pp. 295-304.

50. Granados D.P., Sriranganadane D., Daouda T., Zieger A., Laumont C.M., Caron-Lizotte O., Boucher G., Hardy M.P., Gendron P., Cote C., Lemieux S., Thibault P., Perreault C. Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides. Nat. Commun., 2014, Vol. 5, pp. 3600.

51. Hamadani M., Hofmeister C.C., Jansak B., Phillips G., Elder P., Blum W., Penza S., Lin T.S., Klisovic R., Marcucci G., Farag S.S., Devine S.M. Addition of infliximab to standard acute graft-versus-host disease prophylaxis following allogeneic peripheral blood cell transplantation. Biol. Blood Marrow Transplant., 2008, Vol. 14, pp. 783-789.

52. Hambach L., Goulmy E. Immunotherapy of cancer through targeting of minor histocompatibility antigens. Curr. Opin. Immunol., 2005, Vol. 17, pp. 202-210.

53. He S., Cao Q., Qiu Y., Mi J., Zhang J.Z., Jin M., Ge H., Emerson S.G., Zhang Y., Zhang Y.A new approach to the blocking of alloreactive T cell-mediated graft-versus-host disease by in vivo administration of anti-CXCR3 neutralizing antibody. J. Immunol., 2008, Vol. 181, pp. 7581-7592.

54. Heemskerk M.B., Cornelissen J.J., Roelen D.L., van Rood J.J., Claas F.H., Oudshoorn M. Highly diverged MHC class I mismatches are acceptable for haematopoietic stem cell transplantation. Bone Marrow Transplant., 2007, Vol. 40, pp. 193-200.

55. Heemskerk M.B., van Walraven S.M., Cornelissen J.J., Barge R.M., Bredius R.G., Egeler R.M., Tj Lie J.L., Revesz T., Sintnicolaas K., Wulffraat N.M., Donker A.E., Hoogerbrugge P.M., van Rood J.J., Claas F.H., Oudshoorn M. How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more! Bone Marrow Transplant., 2005, Vol. 35, pp. 645-652.

56. Hofer T., Krichevsky O., Altan-Bonnet G. Competition for IL-2 between Regulatory and Effector T Cells to Chisel Immune Responses. Front. Immunol., 2012, Vol. 3, p. 268.

57. Hutchinson M. Natalizumab: A new treatment for relapsing remitting multiple sclerosis. Ther. Clin. Risk Manag., 2007, Vol. 3, pp. 259-268.

58. Inamoto Y., Murata M., Katsumi A., Kuwatsuka Y., Tsujimura A., Ishikawa Y., Sugimoto K., Onizuka M., Terakura S., Nishida T., Kanie T., Taji H., Iida H., Suzuki R., Abe A., Kiyoi H., Matsushita T., Miyamura K., Kodera Y., Naoe T. Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD. Bone Marrow Transplant., 2010, Vol. 45, pp. 363-369.

59. Israeli M., Roelen D.L., Carrington M., Petersdorf E.W., Claas F.H., Haasnoot G.W., Oudshoorn M. Association between CTL Precursor Frequency to HLA-C Mismatches and HLA-C Antigen Cell Surface Expression. Front. Immunol., 2014, Vol. 5, pp. 547.

60. Jenq R.R., Ubeda C., Taur Y., Menezes C.C., Khanin R., Dudakov J.A., Liu C., West M.L., Singer N.V., Equinda M.J., Gobourne A., Lipuma L., Young L.F., Smith O.M., Ghosh A., Hanash A.M., Goldberg J.D., Aoyama K., Blazar B.R., Pamer E.G., van den Brink M.R. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J. Exp. Med., 2012, Vol. 209, pp. 903-911.

61. Jiang Z., Podack E., Levy R.B. Major histocompatibility complex-mismatched allogeneic bone marrow transplantation using perforin and/or Fas ligand double-defective CD4(+) donor T cells: involvement of cytotoxic function by donor lymphocytes prior to graft-versus-host disease pathogenesis. Blood, 2001, Vol. 98, pp. 390-397.

62. Kagi D., Ledermann B., Burki K., Seiler P., Odermatt B., Olsen K.J., Podack E.R., Zinkernagel R.M., Hengartner H. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature, 1994, Vol. 369, pp. 31-37.

63. Kappel L.W., Goldberg G.L., King C.G., Suh D.Y., Smith O.M., Ligh C., Holland A.M., Grubin J., Mark N.M., Liu C., Iwakura Y., Heller G., van den Brink M.R. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood, 2009, Vol. 113, pp. 945-952.

64. Karabon L., Wysoczanska B., Bogunia-Kubik K., Suchnicki K., Lange A. IL-6 and IL-10 promoter gene polymorphisms of patients and donors of allogeneic sibling hematopoietic stem cell transplants associate with the risk of acute graft-versus-host disease. Hum. Immunol., 2005, Vol. 66, pp. 700-710.

65. Kawase T., Morishima Y., Matsuo K., Kashiwase K., Inoko H., Saji H., Kato S., Juji T., Kodera Y., Sasazuki T., Japan Marrow Donor P. High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism. Blood, 2007, Vol. 110, pp. 2235-2241.

66. Keever C.A., Leong N., Cunningham I., Copelan E.A., Avalos B.R., Klein J., Kapoor N., Adams P.W., Orosz C.G., Tutschka P.J. HLA-B44-directed cytotoxic T cells associated with acute graft-versus-host disease following unrelated bone marrow transplantation. Bone Marrow Transplant., 1994, Vol. 14, pp. 137-145.

67. Kekre N., Antin J.H. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood, 2014, Vol. 124, pp. 334-343.

68. Koreth J., Matsuoka K., Kim H.T., McDonough S.M., Bindra B., Alyea E.P., Armand P., Cutler C., Ho V.T., Treister N.S., Bienfang D.C., Prasad S., Tzachanis D., Joyce R.M., Avigan D.E., Antin J.H., Ritz J., Soiffer R.J. Interleukin-2 and regulatory T cells in graft-versus-host disease. N. Engl. J. Med., 2011, Vol. 365, pp. 2055-2066.

69. Krenge W., Ferrara J.L. Graft-versus-host disease and the Th1/Th2 paradigm. Immunol. Res., 1996, Vol. 15, pp. 50-73.

70. Kumanovics A., Takada T., Lindahl K.F. Genomic organization of the mammalian MHC. Annu Rev. Immunol., 2003, Vol. 21, pp. 629-657.

71. Kuzmina L.A., Petinati N.A., Shipounova I.N., Sats N.V., Bigildeev A.E., Zezina E.A., Popova M.D., Drize N.J., Parovichnikova E.N., Savchenko V.G. Analysis of multipotent mesenchymal stromal cells used for acute graft-versus-host disease prophylaxis. Eur. J. Haematol., 2015.

72. Lang P., Teltschik H.M., Feuchtinger T., Muller I., Pfeiffer M., Schumm M., Ebinger M., Schwarze C.P., Gruhn B., Schrauder A., Albert M.H., Greil J., Urban C., Handgretinger R. Transplantation of CD3/CD19 depleted allografts from haploidentical family donors in paediatric leukaemia. Br. J. Haematol., 2014, Vol. 165, pp. 688-698.

73. Lee S.J., Klein J., Haagenson M., Baxter-Lowe L.A., Confer D.L., Eapen M., Fernandez-Vina M., Flomenberg N., Horowitz M., Hurley C.K., Noreen H., Oudshoorn M., Petersdorf E., Setterholm M., Spellman S., Weisdorf D., Williams T.M., Anasetti C. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood, 2007, Vol. 110, pp. 4576-4583.

74. Lee Y.J., Chung D., Xiao K., Papadopoulos E.B., Barker J.N., Small T.N., Giralt S.A., Zheng J., Jakubowski A.A., Papanicolaou G.A. Adenovirus viremia and disease: comparison of T cell-depleted and conventional hematopoietic stem cell transplantation recipients from a single institution. Biol. Blood Marrow Transplant., 2013, Vol. 19, pp. 387-392.

75. Ley K. The role of selectins in inflammation and disease. Trends Mol. Med., 2003, Vol. 9, pp. 263-268.

76. Lu S.X., Holland A.M., Na I.K., Terwey T.H., Alpdogan O., Bautista J.L., Smith O.M., Suh D., King C., Kochman A., Hubbard V.M., Rao U.K., Yim N., Liu C., Laga A.C., Murphy G., Jenq R.R., Zakrzewski J.L., Penack O., Dykstra L., Bampoe K., Perez L., Furie B., Furie B., van den Brink M.R. Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease. J. Immunol., 2010, Vol. 185, pp. 1912-1919.

77. Lu S.Y., Liu K.Y., Liu D.H., Xu L.P., Huang X.J. High frequencies of CD62L(+) naive regulatory T cells in allografts are associated with a low risk of acute graft-versus-host disease following unmanipulated allogeneic haematopoietic stem cell transplantation. Clin. Exp. Immunol., 2011, Vol. 165, pp. 264-277.

78. Ma J.D., Lee K.C., Kuo G.M. HLA-B*5701 testing to predict abacavir hypersensitivity. PLoS Curr., 2010, Vol. 2, p. RRN1203.

79. Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol., 2004, Vol. 25, pp. 677-686.

80. Mapara M.Y., Kim Y.M., Wang S.P., Bronson R., Sachs D.H., Sykes M. Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Blood, 2002, Vol. 100, pp. 1903-1909.

81. Maris M.B., Niederwieser D., Sandmaier B.M., Storer B., Stuart M., Maloney D., Petersdorf E., McSweeney P., Pulsipher M., Woolfrey A., Chauncey T., Agura E., Heimfeld S., Slattery J., Hegenbart U., Anasetti C., Blume K., Storb R. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood, 2003, Vol. 102, pp. 2021-2030.

82. Massenkeil G., Rackwitz S., Genvresse I., Rosen O., Dorken B., Arnold R. Basiliximab is well tolerated and effective in the treatment of steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation. Bone Marrow Transplant., 2002, Vol. 30, pp. 899-903.

83. Middleton P.G., Taylor P.R., Jackson G., Proctor S.J., Dickinson A.M. Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants. Blood, 1998, Vol. 92, pp. 3943-3948.

84. Minculescu L., Sengelov H. The role of gamma delta T cells in haematopoietic stem cell transplantation. Scand. J. Immunol., 2015, Vol. 81, pp. 459-468.

85. Miwa K., Hashimoto H., Yatomi T., Nakamura N., Nagata S., Suda T. Therapeutic effect of an anti-Fas ligand mAb on lethal graft-versus-host disease. Int. Immunol., 1999, Vol. 11, pp. 925-931.

86. Mohty M., Blaise D., Faucher C., Vey N., Bouabdallah R., Stoppa A.M., Viret F., Gravis G., Olive D., Gaugler B. Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Blood, 2005, Vol. 106, pp. 4407-4411.

87. Morris G.P., Uy G.L., Donermeyer D., Dipersio J.F., Allen P.M. Dual receptor T cells mediate pathologic alloreactivity in patients with acute graft-versus-host disease. Sci Transl. Med., 2013, Vol. 5, p. 188ra174.

88. Muller W.A. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol., 2003, Vol. 24, pp. 327-334.

89. Nagata S. Apoptosis by death factor. Cell, 1997, Vol. 88, pp. 355-365.

90. Naik S., Heslop H.E. Engineering haploidentical transplants. Bone Marrow Transplant., 2015, Vol. 50, no. 7, pp. 884-885.

91. Ng P.C., Henikoff S. Predicting the effects of amino acid substitutions on protein function. Annu Rev. Genomics Hum. Genet., 2006, Vol. 7, pp. 61-80.

92. Ni P.P., Solomon B., Hsieh C.S., Allen P.M., Morris G.P. The ability to rearrange dual TCRs enhances positive selection, leading to increased Allo- and Autoreactive T cell repertoires. J. Immunol., 2014, Vol. 193, pp. 1778-1786.

93. Norton J., al-Saffar N., Sloane J.P. Adhesion molecule expression in human hepatic graft-versus-host disease. Bone Marrow Transplant., 1992, Vol. 10, pp. 153-156.

94. Panoskaltsis-Mortari A., Hermanson J.R., Haddad I.Y., Wangensteen O.D., Blazar B.R. Intercellular adhesion molecule-I (ICAM-I, CD54) deficiency segregates the unique pathophysiological requirements for generating idiopathic pneumonia syndrome (IPS) versus graft-versus-host disease following allogeneic murine bone marrow transplantation. Biol. Blood Marrow Transplant., 2001, Vol. 7, pp. 368-377.

95. Penack O., Holler E., van den Brink M.R. Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Blood, 2010, Vol. 115, pp. 1865-1872.

96. Petersdorf E.W., Gooley T.A., Malkki M., Bacigalupo A.P., Cesbron A., Du Toit E., Ehninger G., Egeland T., Fischer G.F., Gervais T., Haagenson M.D., Horowitz M.M., Hsu K., Jindra P., Madrigal A., Oudshoorn M., Ringden O., Schroeder M.L., Spellman S.R., Tiercy J.M., Velardi A., Witt C.S., O’Huigin C., Apps R., Carrington M. International Histocompatibility Working Group in Hematopoietic Cell. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation. Blood, 2014, Vol. 124, pp. 3996-4003.

97. Raiola A.M., Dominietto A., di Grazia C., Lamparelli T., Gualandi F., Ibatici A., Bregante S., Van Lint M.T., Varaldo R., Ghiso A., Gobbi M., Carella A.M., Signori A., Galaverna F., Bacigalupo A. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol. Blood Marrow Transplant., 2014, Vol. 20, pp. 1573-1579.

98. Ramshaw H.S., Crittenden R.B., Dooner M., Peters S.O., Rao S.S., Quesenberry P.J. High levels of engraftment with a single infusion of bone marrow cells into normal unprepared mice. Biol. Blood Marrow Transplant., 1995, Vol. 1, pp. 74-80.

99. Rubio M.T., Kim Y.M., Sachs T., Mapara M., Zhao G., Sykes M. Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-gamma. Blood, 2003, Vol. 102, pp. 2300-2307.

100. Ruggeri L., Capanni M., Urbani E., Perruccio K., Shlomchik W.D., Tosti A., Posati S., Rogaia D., Frassoni F., Aversa F., Martelli M.F., Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science, 2002, Vol. 295, pp. 2097-2100.

101. Sackstein R.A revision of Billingham’s tenets: the central role of lymphocyte migration in acute graft-versushost disease. Biol. Blood Marrow Transplant., 2006, Vol. 12, pp. 2-8.

102. Sarantopoulos S., Blazar B.R., Cutler C., Ritz J. B cells in chronic graft-versus-host disease. Biol. Blood Marrow Transplant., 2015, Vol. 21, pp. 16-23.

103. Schiltz P.M., Giorno R.C., Claman H.N. Increased ICAM-1 expression in the early stages of murine chronic graft-versus-host disease. Clin. Immunol. Immunopathol., 1994, Vol. 71, pp. 136-141.

104. Schmaltz C., Alpdogan O., Horndasch K.J., Muriglan S.J., Kappel B.J., Teshima T., Ferrara J.L., Burakoff S.J., van den Brink M.R. Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versushost disease and graft-versus-leukemia effect. Blood, 2001, Vol. 97, pp. 2886-2895.

105. Schmitt N., Ueno H. Regulation of human helper T cell subset differentiation by cytokines. Curr. Opin. Immunol., 2015, Vol. 34, pp. 130-136.

106. Schneidawind D., Pierini A., Negrin R.S. Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation. Blood, 2013, Vol. 122, pp. 3116-3121.

107. Scott B.L., Sandmaier B.M. Outcomes with myeloid malignancies. Hematology Am. Soc. Hematol. Educ. Program., 2006, Vol., pp. 381-389.

108. Sellge G., Kufer T.A. PRR-signaling pathways: Learning from microbial tactics. Semin. Immunol., 2015, Vol. 27, pp. 75-84.

109. Serody J.S., Burkett S.E., Panoskaltsis-Mortari A., Ng-Cashin J., McMahon E., Matsushima G.K., Lira S.A., Cook D.N., Blazar B.R. T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease. Blood, 2000, Vol. 96, pp. 2973-2980.

110. Serody J.S., Hill G.R. The IL-17 differentiation pathway and its role in transplant outcome. Biol. Blood Marrow Transplant., 2012, Vol. 18, pp. S56-61.

111. Shipounova I.N., Petinati N.A., Bigildeev A.E., Zezina E.A., Drize N.I., Kuzmina L.A., Parovichnikova E.N., Savchenko V.G. Analysis of results of acute graft-versus-host disease prophylaxis with donor multipotent mesenchymal stromal cells in patients with hemoblastoses after allogeneic bone marrow transplantation. Biochemistry (Mosc.), 2014, Vol. 79, pp. 1363-1370.

112. Silva I.A., Olkiewicz K., Askew D., Fisher J.M., Chaudhary M.N, Vannella K.M., Deurloo D.T., Choi S.W., Pierce E.M., Clouthier S.G., Liu C., Cooke K.R. Secondary lymphoid organs contribute to, but are not required for the induction of graft-versus-host responses following allogeneic bone marrow transplantation: a shifting paradigm for T cell allo-activation. Biol. Blood Marrow Transplant., 2010, Vol. 16, pp. 598-611.

113. Spierings E., Kim Y.H., Hendriks M., Borst E., Sergeant R., Canossi A., Oudshoorn M., Loiseau P., Dolstra H., Markiewicz M., Leffell M.S., Pereira N., Kircher B., Turpeinen H., Eliaou J.F., Gervais T., Laurin D., Enczmann J., Martinetti M., Thomson J., Oguz F., Santarone S., Partanen J., Siekiera U., Alessandrino E.P., Kalayoglu S., Brand R., Goulmy E. Multicenter analyses demonstrate significant clinical effects of minor histocompatibility antigens on GvHD and GvL after HLA-matched related and unrelated hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant., 2013, Vol. 19, pp. 1244-1253.

114. Steinmetz O.M., Turner J.E., Paust H.J., Lindner M., Peters A., Heiss K., Velden J., Hopfer H., Fehr S., Krieger T., Meyer-Schwesinger C., Meyer T.N., Helmchen U., Mittrucker H.W., Stahl R.A., Panzer U. CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis. J. Immunol., 2009, Vol. 183, pp. 4693-4704.

115. Stewart F.M., Crittenden R.B., Lowry P.A., Pearson-White S., Quesenberry P.J. Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice. Blood, 1993, Vol. 81, pp. 2566-2571.

116. Strawbridge A.B., Blum J.S. Autophagy in MHC class II antigen processing. Curr. Opin. Immunol., 2007, Vol. 19, pp. 87-92.

117. Sureda A., Bader P., Cesaro S., Dreger P., Duarte R.F., Dufour C., Falkenburg J.H., Farge-Bancel D.,

118. Gennery A., Kroger N., Lanza F., Marsh J.C., Nagler A., Peters C., Velardi A., Mohty M., Madrigal A. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant., 2015, Vol. 50, pp. 1037-1056 .

119. Tanaka T., Ohtsuka Y., Yagita H., Shiratori Y., Omata M., Okumura K. Involvement of alpha 1 and alpha 4 integrins in gut mucosal injury of graft-versus-host disease. Int. Immunol., 1995, Vol. 7, pp. 1183-1189.

120. Terwey T.H., Kim T.D., Kochman A.A., Hubbard V.M., Lu S., Zakrzewski J.L., Ramirez-Montagut T.,

121. Eng J.M., Muriglan S.J., Heller G., Murphy G.F., Liu C., Budak-Alpdogan T., Alpdogan O., van den Brink M.R. CCR2 is required for CD8-induced graft-versus-host disease. Blood, 2005, Vol. 106, pp. 3322-3330.

122. Teshima T., Maeda Y., Ozaki K. Regulatory T cells and IL-17-producing cells in graft-versus-host disease. Immunotherapy, 2011, Vol. 3, pp. 833-852.

123. Teshima T., Ordemann R., Reddy P., Gagin S., Liu C., Cooke K.R., Ferrara J.L. Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nat. Med., 2002, Vol. 8, pp. 575-581.

124. Thomas E.D., Buckner C.D., Banaji M., Clift R.A., Fefer A., Flournoy N., Goodell B.W., Hickman R.O.,

125. Lerner K.G., Neiman P.E., Sale G.E., Sanders J.E., Singer J., Stevens M., Storb R., Weiden P.L. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood, 1977, Vol. 49, pp. 511-533.

126. Valdor R., Macian F. Induction and stability of the anergic phenotype in T cells. Semin. Immunol., 2013, Vol. 25, pp. 313-320.

127. Vincent K., Roy D.C., Perreault C. Next-generation leukemia immunotherapy. Blood, 2011, Vol. 118, pp. 2951-2959.

128. Waldman E., Lu S.X., Hubbard V.M., Kochman A.A., Eng J.M., Terwey T.N., Muriglan S.J., Kim T.D., Heller G., Murphy G.F., Liu C., Alpdogan O., van den Brink M.R.. Absence of beta7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood, 2006, Vol. 107, pp. 1703-1711.

129. Wang J.Z., Liu K.Y., Xu L.P., Liu D.H., Han W., Chen H., Chen Y.H., Zhang X.H., Zhao T., Wang Y., Huang X.J. Basiliximab for the treatment of steroid-refractory acute graft-versus-host disease after unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation. Transplant. Proc., 2011, Vol. 43, pp. 1928- 1933.

130. Warlick E.D., Peffault de Latour R., Shanley R., Robin M., Bejanyan N., Xhaard A., Brunstein C., Sicre de Fontbrune F., Ustun C., Weisdorf D.J., Socie G. Allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia: similar outcomes regardless of donor type. Biol. Blood Marrow Transplant., 2015, Vol. 21, pp. 357-363.

131. Wilson N.S., Villadangos J.A. Regulation of antigen presentation and cross-presentation in the dendritic cell network: facts, hypothesis, and immunological implications. Adv. Immunol., 2005, Vol. 86, pp. 241-305.

132. Wysocki C.A., Jiang Q., Panoskaltsis-Mortari A., Taylor P.A., McKinnon K.P., Su L., Blazar B.R., Serody J.S. Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease. Blood, 2005, Vol. 106, pp. 3300-3307.

133. Wysocki C.A., Panoskaltsis-Mortari A., Blazar B.R., Serody J.S. Leukocyte migration and graft-versus-host disease. Blood, 2005, Vol. 105, pp. 4191-4199.

134. Xun C.Q., Thompson J.S., Jennings C.D., Brown S.A., Widmer M.B. Effect of total body irradiation, busulfancyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice. Blood, 1994, Vol. 83, pp. 2360-2367.

135. Zhang L., Zhang Y.Z. Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status. Cancer Biol. Med., 2013, Vol. 10, pp. 1-9.

136. Zheng H., Matte-Martone C., Li H., Anderson B.E., Venketesan S., Sheng Tan H., Jain D., McNiff J., Shlomchik W.D. Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease. Blood, 2008, Vol. 111, pp. 2476-2484.

137. Zhou L., Askew D., Wu C., Gilliam A.C. Cutaneous gene expression by DNA microarray in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J. Invest. Dermatol., 2007, Vol. 127, pp. 281-292.

138. Zino E., Frumento G., Marktel S., Sormani M.P., Ficara, Di Terlizzi S., Parodi A.M., Sergeant R., Martinetti M., Bontadini A., Bonifazi F., Lisini D., Mazzi B., Rossini S., Servida P., Ciceri F., Bonini C., Lanino E., Bandini G., Locatelli F., Apperley J., Bacigalupo A., Ferrara G.B., Bordignon C., Fleischhauer K. A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation.

139. Blood, 2004, Vol. 103, pp. 1417-1424.


Для цитирования:


Ефимов Г.А., Вдовин А.С., Григорьев А.А., Филькин С.Ю., Быкова Н.А., Савченко В.Г. ИММУНОБИОЛОГИЯ ОСТРОЙ РЕАКЦИИ «ТРАНСПЛАНТАТ ПРОТИВ ХОЗЯИНА». Медицинская иммунология. 2015;17(6):499-516. https://doi.org/10.15789/1563-0625-2015-6-499-516

For citation:


Efimov G.A., Vdovin A.S., Grigoryev A.A., Filkin S.Y., Bykova N.A., Savchenko V.G. IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE. Medical Immunology (Russia). 2015;17(6):499-516. (In Russ.) https://doi.org/10.15789/1563-0625-2015-6-499-516

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