THE ROLE OF REGULATORY T CELLS IN THE DEVELOPMENT OF AUTOIMMUNE PROCESS IN MULTIPLE SCLEROSIS
- Authors: Eliseeva D.D.1, Zavalishin I.A.1, Karaulov A.V.2, Bykovskaya S.N.3
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Affiliations:
- Research Center of Neurology RAMS, 6 neurological department
- Russian State Medical University, Front cell technologies and regenerative medicine
- First Moscow State Medical University I.M. Sechenov, Department of Clinical Immunology and Allergy Summary
- Issue: Vol 67, No 3 (2012)
- Pages: 68-74
- Section: SHORT MESSAGES
- Published: 23.03.2012
- URL: https://vestnikramn.spr-journal.ru/jour/article/view/335
- DOI: https://doi.org/10.15690/vramn.v67i3.188
- ID: 335
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Full Text
Abstract
In the maintenance of immunological tolerance important role belongs to the recently discovered population of regulatory T-cells CD4 + CD25 + FoxP3 +. These cells have potential in suppressing pathologic immune responses observed at various autoimmune diseases including multiple sclerosis. We have shown a reduction in the number and functional activity of T-reg in peripheral blood of patients with multiple sclerosis in the acute stage, the increase in their number during remission, duration of the relationship of the autoimmune process and the degree of disability of patients with the contents of T-reg. The possibility of using the grown ex vivo T-reg for the correction of immunopathological process in multiple sclerosis.
About the authors
D. D. Eliseeva
Research Center of Neurology RAMS, 6 neurological department
Author for correspondence.
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
I. A. Zavalishin
Research Center of Neurology RAMS, 6 neurological department
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
A. V. Karaulov
Russian State Medical University, Front cell technologies and regenerative medicine
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
S. N. Bykovskaya
First Moscow State Medical University I.M. Sechenov, Department of Clinical Immunology and Allergy Summary
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
References
- Zavalishin I.A., Golovkin V.I. Rasseyannyi skleroz. Izbrannye voprosy teorii i praktiki. Moskva. 2000. 637 s.
- Gusev E.I., Boiko A.N., Zavalishin I.A. Epidemiologicheskoe issledovanie rasseyannogo skleroza. Metodicheskie rekomendacii MZ RF № 2003/82. Moskva. 2003. 80 s.
- Gusev E.I., Boiko A.N. Rasseyannyi skleroz: dostijeniya desyatiletiya. Jurn nevrol. i psihiatrii. Spec. vypusk «Rasseyannyi skleroz». 2007; 4: 4–13.
- 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.
- Kerschensteiner M., Misgeld T. Cellular imaging in the nervous system. Dtsch Med Wochenschr. 2007; 132 (47): 2529–2533.
- 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.
- Jiang S., Lechler R.I., He X.S., Huang J.F. Regulatory T cells and transplantation tolerance. Hum Immunol. 2006; 67 (10): 765–776.
- 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.
- 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.
- Nasonov E.L., Bykovskaya S.N. T-regulyatornye kletki pri autoimmunnyh revmaticheskih zabolevaniyah. Vestnik RAMN. 2006; 9–10: 74–82.
- 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.
- 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.
- 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.
- Hori S., Takahashi T., Sakaguchi S. Control of autoimmunity by naturally arising regulatory CD4+ T-cells. Adv Immunol. 2003; 81: 331–371.
- 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.
- 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.
- 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.
- Vignali D.A., Collison L.W., Workman C.J. How regulatory T-cells work. Nat Rev Immunol. 2008; 8 (7): 523–532.
- Roncarolo M.G., Battaglia M., Gregori S. The role of interleukin 10 in the control of autoimmunity. J Autoimmun. 2003; 20 (4): 269–272.
- 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.
- 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.
- 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.
- Mosser D.M., Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008; 226: 205–218.
- 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.
- 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.
- 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.
- 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.
- 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.
- Toda A., Piccirillo C.A. Development and function of naturally occurring CD4+CD25+ regulatory T-cells. J Leukoc Biol. 2006; 80 (3): 458–470.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Dejaco C., Duftner C., Grubeck-Loebenstein B., Schirmer M. Imbalance of regulatory T-cells in human autoimmune diseases. Immunology. 2006; 117 (3): 289–300.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Huan J. Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res. 2005; 81: 45–52.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Baecher-Allan C., Hafler D.A. Human regulatory T-cells and their role in autoimmune disease. Immunol Rev. 2006; 212: 203–216.
- 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.
- 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.
- 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.
- 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.