РОЛЬ РЕГУЛЯТОРНЫХ Т-КЛЕТОК В РАЗВИТИИ АУТОИММУННЫХ НАРУШЕНИЙ ПРИ РАССЕЯННОМ СКЛЕРОЗЕ

Обложка


Цитировать

Полный текст

Аннотация

В процессах поддержания иммунологической толерантности важная роль принадлежит недавно открытой популяции регуляторных Т-клеток CD4+CD25+FoxP3+ (Т-reg).  Эти клетки обладают огромным потенциалом в подавлении патологического иммунного ответа, наблюдающегося при различных аутоиммунных заболеваниях, в том числе при рассеянном склерозе. Продемонстрировано  снижение числа и функциональной активности Т-reg в периферической крови  больных рассеянным склерозом в стадии обострения, увеличение их количества при ремиссии заболевания, связь длительности аутоиммунного процесса и степени инвалидизации больных с количеством  Т-reg.  Показана возможность использования выращенных ex vivo Т-reg для коррекции иммунопатологических нарушений при рассеянном склерозе.

Об авторах

Д. Д. Елисеева

ФГБУ «Научно-исследовательский институт неврологии» РАМН, Москва

Автор, ответственный за переписку.
Email: ddeliseeva@gmail.com
кандидат медицинских наук, младший научный сотрудник лаборатории клинических исследований, врач-невролог 6-го неврологического отделения ФГБУ «НЦН» РАМН Адрес: 125367, Москва, Волоколамское шоссе, д. 80 Тел.: (495) 490-24-13, факс: (495) 490-28-73 Россия

И. А. Завалишин

ФГБУ «Научно-исследовательский институт неврологии» РАМН, Москва

Email: 6otdelen@gmail.com
доктор медицинских наук, профессор, руководитель 6-го неврологического отделения ФГБУ «НЦН» РАМН Адрес: 125367, Москва, Волоколамское шоссе, д. 80 Тел.: (495) 490-21-55, факс: (495) 490-28-73 Россия

А. В. Караулов

ГБОУ ВПО Первый Московский государственный медицинский университет имени И.М. Сеченова, Москва

Email: drkaraulov@mail.ru
доктор медицинских наук, чл.-корр. РАМН, заведующий кафедрой клинической иммунологии и аллергологии факультета послевузовского профессионального образования ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Адрес: 119435, Москва, ул. Б. Пироговская д. 2, к. 6 Тел.: (495) 395-64-97 Россия

С. Н. Быковская

ГБОУ Российский национальный исследовательский медицинский университет имени Н.И. Пирогова, Москва

Email: sbykovskaia@gmail.com
доктор медицинских наук, профессор, заведующая Отделом клеточных технологий и регенеративной медицины Российского национального исследовательского медицинского университета (РНИМУ) им. Н.И. Пирогова Адрес: 117997, Москва, ул. Островитянова, д. 1 Тел.: (495) 434-14-44 Россия

Список литературы

  1. Zavalishin I.A., Golovkin V.I. Rasseyannyi skleroz. Izbrannye voprosy teorii i praktiki. Moskva. 2000. 637 s.
  2. Gusev E.I., Boiko A.N., Zavalishin I.A. Epidemiologicheskoe issledovanie rasseyannogo skleroza. Metodicheskie rekomendacii MZ RF № 2003/82. Moskva. 2003. 80 s.
  3. Gusev E.I., Boiko A.N. Rasseyannyi skleroz: dostijeniya desyatiletiya. Jurn nevrol. i psihiatrii. Spec. vypusk «Rasseyannyi skleroz». 2007; 4: 4–13.
  4. Fletcher J.M., Lalor S.J., Sweeney C.M. et al. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010; 162 (1): 1–11.
  5. Kerschensteiner M., Misgeld T. Cellular imaging in the nervous system. Dtsch Med Wochenschr. 2007; 132 (47): 2529–2533.
  6. Merkulov Yu.A., Zavalishin I.A., Merkulova D.M. Rol’ aksonopatii v mehanizmah razvitiya demieliniziruyuschih processov v central’noi i perifericheskoi nervnoi sisteme. Jurn. nevrologii i psihiatrii im. S.S. Korsakova. 2007; 3: 26–30.
  7. Jiang S., Lechler R.I., He X.S., Huang J.F. Regulatory T cells and transplantation tolerance. Hum Immunol. 2006; 67 (10): 765–776.
  8. Hall B.M., Pearce N.W., Gurley K.E., Dorsch S.E. Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action. J. Exp. Med. 1990; 171: 141–157.
  9. Sakaguchi S., Sakaguchi N., Asano M. et al. Immunologic selftolerans maintained by activated T cells expressing IL-2 receptor alfa-chains (CD25). Breakdown of a single mechanism of selftolerance causes various autoimmune diseases. J. Immunol. 1995; 155 (3): 1151–1164.
  10. Nasonov E.L., Bykovskaya S.N. T-regulyatornye kletki pri autoimmunnyh revmaticheskih zabolevaniyah. Vestnik RAMN. 2006; 9–10: 74–82.
  11. Vorob’ev A.A., Bykovskaya S.Yu., Pashkov E.P., Bykov A.S. Rol’ kletok-regulyatorov CD4+CD25+ v razvitii hronicheskih infekcionnyh zabolevanii. Vestnik RAMN. 2006; 9–10: 24–29.
  12. Piccirillo C.A., Shevach E.M. Naturally-occurring CD4+CD25+ immunoregulatory T-cells: central players in the arena of peripheral tolerance. Semin Immunol. 2004; 16 (2): 81–88.
  13. Fourcade J., Sun Z., Kudela P. et al. Human tumor antigen-specific helper and regulatory T-cells share common epitope specificity but exhibit distinct T-cell repertoire. J Immunol. 2010; 184 (12): 6709–6718.
  14. Hori S., Takahashi T., Sakaguchi S. Control of autoimmunity by naturally arising regulatory CD4+ T-cells. Adv Immunol. 2003; 81: 331–371.
  15. Sanchez J., Casano J., Alvarez M.A. et al. Kinetic of regulatory CD25 high and activated CD134+ (OX40) T lymphocytes during acute and chronic graft-versus-host disease after allogeneic bone marrow transplantation. Br J Haematol. 2004; 126 (5): 697–703.
  16. Walker M.R., Kasprowicz D.J., Gersuk V.H. et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T-cells. J Clin Invest. 2003; 112 (9): 1437–1443.
  17. Gambineri E., Torgerson T.R., Ochs H.D. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol. 2003; 15 (4): 430–435.
  18. Vignali D.A., Collison L.W., Workman C.J. How regulatory T-cells work. Nat Rev Immunol. 2008; 8 (7): 523–532.
  19. Roncarolo M.G., Battaglia M., Gregori S. The role of interleukin 10 in the control of autoimmunity. J Autoimmun. 2003; 20 (4): 269–272.
  20. Li M.O., Wan Y.Y., Flavell R.A. T cell-produced transforming growth factor-beta1 controls T-cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity. 2007; 26 (5): 579–591.
  21. Kingsley C.I., Karim M., Bushell A.R., Wood K.J. CD25+CD4+ regulatory T-cells prevent graft rejection: CTLA-4- and IL-10- dependent immunoregulation of alloresponses. J Immunol. 2002; 168 (3): 1080–1086.
  22. Belkaid Y., Piccirillo C.A., Mendez S., Shevach E.M. et al. CD4+CD25+ regulatory T-cells control Leishmania major persistence and immunity. Nature. 2002; 420 (6915): 502–507.
  23. Mosser D.M., Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008; 226: 205–218.
  24. Selvaraj R.K., Geiger T.L. Mitigation of experimental allergic encephalomyelitis by TGF-beta induced Foxp3+ regulatory T lymphocytes through the induction of anergy and infectious tolerance. J Immunol. 2008; 180 (5): 2830–2838.
  25. Collison L.W., Pillai M.R., Chaturvedi V., Vignali D.A. Regulatory T-cell suppression is potentiated by target T-cells in a cell contact, IL-35- and IL-10-dependent manner. J Immunol. 2009; 182 (10): 6121–6128.
  26. Takahashi T., Tagami T., Yamazaki S. et al. Immunologic selftolerance maintained by CD25(+)CD4(+) regulatory T-cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med. 2000; 192 (2): 303–310.
  27. Borsellino G., Kleinewietfeld M., Di Mitri D. et al. Expression of ectonucleotidase CD39 by Foxp3+ T-reg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007; 110 (4): 1225–1232.
  28. Luhder F., Hoglund P., Allison J.P. et al. Cytotoxic T lymphocyteassociated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. J Exp Med. 1998; 187 (3): 427–432.
  29. Toda A., Piccirillo C.A. Development and function of naturally occurring CD4+CD25+ regulatory T-cells. J Leukoc Biol. 2006; 80 (3): 458–470.
  30. Fu S., Zhang N., Yopp A.C., Chen D. et al. TGF-beta induces Foxp3 + T-regulatory cells from CD4 + CD25 – precursors. Am J Transplant. 2004; 4 (10): 1614–1627.
  31. Pohlers D., Beyer A., Koczan D. et al. Constitutive upregulation of the transforming growth factor-beta pathway in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther. 2007; 9 (3): R59.
  32. Lyssuk E.Y., Torgashina A.V., Soloviev S.K., Nassonov E.L. Reduced number and function of CD4+CD25 high FoxP3+ regulatory T-cells in patients with systemic lupus erythematosus. Adv Exp Med Biol. 2007; 601: 113–119.
  33. Xu Y.Q., Gao Y.D., Yang J., Guo W. A defect of CD4+CD25+ regulatory T-cells in inducing interleukin-10 production from CD4+ T-cells under CD46 costimulation in asthma patients. J Asthma. 2010; 47 (4): 367–373.
  34. Sugiyama H., Gyulai R., Toichi E. et al. Dysfunctional blood and target tissue CD4+CD25 high regulatory T-cells in psoriasis: mechanism underlying unrestrained pathogenic effector T-cell proliferation. J Immunol. 2005; 174 (1): 164–173.
  35. Verhagen J., Akdis M., Traidl-Hoffmann C. et al. Absence of T-regulatory cell expression and function in atopic dermatitis skin. J Allergy Clin Immunol. 2006; 117 (1): 176–183.
  36. Dejaco C., Duftner C., Grubeck-Loebenstein B., Schirmer M. Imbalance of regulatory T-cells in human autoimmune diseases. Immunology. 2006; 117 (3): 289–300.
  37. Balandina A., Lecart S., Dartevelle P. et al. Functional defect of regulatory CD4(+)CD25+ T- cells in the thymus of patients with autoimmune myasthenia gravis. Blood. 2005; 105 (2): 735–741.
  38. Grindebacke H., Wing K., Andersson A.C., Suri-Payer E. Defective suppression of Th2 cytokines by CD4CD25 regulatory T-cells in birch allergics during birch pollen season. Clin Exp Allergy. 2004; 34 (9): 1364–1372.
  39. Zhang X., Reddy J., Ochi H. et al. Recovery from experimental allergic encephalomyelitis is TGF-beta dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T-cells. Int Immunol. 2006; 18 (4): 495–503.
  40. Matsumoto Y., Sakuma H., Kohyama K., Park I.K. Paralysis of CD4(+)CD25(+) regulatory T- cell response in chronic autoimmune encephalomyelitis. J Neuroimmunol. 2007; 187 (1–2): 44–54.
  41. McGeachy M.J., Stephens L.A., Anderton S.M. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. J Immunol. 2005; 175 (5): 3025–3032.
  42. Korn T., Anderson A.C., Bettelli E., Oukka M. The dynamics of effector T-cells and Foxp3+ regulatory T-cells in the promotion and regulation of autoimmune encephalomyelitis. J Neuroimmunol. 2007; 191 (1–2): 51–60.
  43. Beyersdorf N., Gaupp S., Balbach K. et al. Selective targeting of regulatory T-cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis. J Exp Med. 2005; 202 (3): 445–455.
  44. Viglietta V., Baercher-Allan C., Weiner H.L., Haefer D.A. Human CD4+CD25+ regulatory T- cells J. Exp Med. 2004; 199 (7): 971–972.
  45. Huan J. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. 2005; 81: 45–52.
  46. Haas J., Hug A., Viehover A. et al. Reduced suppressive effect of CD4+CD25high regulatory T- cells on the T-cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol. 2005; 35: 3343–3352.
  47. Haas J., Fritzsching B., Trubswetter P. et al. Prevalence of newly generated naive regulatory T- cells (T-reg) is critical for T-reg suppressive function and determines T-reg dysfunction in multiple sclerosis. J Immunol. 2007; 179 (2): 1322–1330.
  48. Martinez-Forero I., Garcia-Munoz R., Martinez-Pasamar S. et al. IL-10 suppressor activity and ex vivo Tr1-cell function are impaired in multiple sclerosis. Eur J Immunol. 2008; 38 (2): 576–586.
  49. Venken K., Hellings N., Hensen K. et al. Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression. J Neurosci Res. 2006; 83 (8): 1432–1446.
  50. Venken K., Hellings N., Thewissen M. et al. Compromised CD4+ CD25(high) regulatory T-cell function in patients with relapsingremitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the singlecell level. Immunology. 2008; 123 (1): 79–89.
  51. Feger U. HLA-G expression defines a novel regulatory T-cell subset present in human peripheral blood and sites of inflammation. Blood. 2007; 110: 568–577.
  52. Airas L., Saraste M., Rinta S. et al. Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells. Clin Exp Immunol. 2008; 151 (2): 235–243.
  53. Fletcher J.M., Lonergan R., Costelloe L. et al. CD39+Foxp3+ regulatory T-cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol. 2009; 183 (11): 7602–7610.
  54. Baecher-Allan C., Hafler D.A. Human regulatory T-cells and their role in autoimmune disease. Immunol Rev. 2006; 212: 203–216.
  55. de Andres C., Aristimuno C., de Las Heras V. et al. Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: an ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis. J Neuroimmunol. 2007; 182 (1–2): 204–211.
  56. Saresella M., Marventano I., Longhi R. et al. CD4+CD25+FoxP3+PD1-regulatory T-cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy. FASEB J. 2008; 22 (10): 3500–3508.
  57. Braitch M., Harikrishnan S., Robins R.A. et al. Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis. Acta Neurol Scand. 2009; 119 (4): 239–245.
  58. Allan S.E., Song-Zhao G.X., Abraham T. et al. Inducible reprogramming of human T-cells into T-reg cells by a conditionally active form of FOXP3. Eur J Immunol. 2008; 38 (12): 3282–3289.

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© Издательство "Педиатръ", 2012



Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах