본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Anti-CD3 Antibody Induces IL-10-producing $CD4^+CD25^+$ Regulatory T Cells, Which Suppress T Cell Response in Rheumatoid Arthritis Patients

Yoon, Bo-Young   (Department of Internal Medicine, Inje Univeresity Ilsan Paik HospitalHH0065933  ); Cho, Mi-La   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  ); Hong, Yeon-Sik   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  ); Jhun, Joo-Yeon   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  ); Park, Mi-Kyung   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  ); Park, Kyung-Su   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  ); Park, Sung-Hwan   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  ); Kim, Ho-Youn   (Division of Rheumatology, Department of Internal Medicine, The Center for Rheumatic Diseases, and The Rheumatism Research Center (RhRC), Catholic Research Institutes of Medical Sciences, Catholic University of KoreaUU0013933  );
  • 초록

    Background: Regulatory T cells (Tregs) have been investigated intensively for some decades. These cells regulate the immune system, prevent overactivated immune responses and can be used therapeutically. For rheumatoid arthritis (RA), understanding the functions and status of Tregs is an important step for understanding immune regulation in this autoimmune disease. Methods: We investigated the percentages, phenotypes and suppressive functions of $CD4^+CD25^+$ Tregs in peripheral blood (PB) of patients with RA. Results: The percentages were higher in the patients (n=12) than in healthy controls (n=10), and the cells expressed the $CD45RB^{low}$ , CTLA-4 and CCR7 phenotypes. We also investigated the expression of Foxp3 and secretion of interleukin (IL)-10 induced $CD4^+CD25^+$ Tcells by anti-CD3 antibody treatment. A suppressive function of the patients' cells was shown through coculture with $CD4^+CD25^-$ T cells in vitro. Conclusion: We suggest that, despite their increased numbers and suppressive function, they manage the ongoing inflammation ineffectively. It might be possible to apply IL-10 to induce the proliferation of IL-10-producing Tregs as therapy for RA.


  • 주제어

    Regulatory T cells .   $CD4^+CD25^+$ cell .   rheumatoid arthritis .   IL-10 .   peripheral blood.  

  • 참고문헌 (32)

    1. Weyand CM: New insight into the pathogenesis of rheumatoid arthritis. Rheumatology 39;3-8, 2000 
    2. Jonuleit H, Schmitt E: The regulatory T cell family: distinct subsets and their interrelations. J Immunol 171 ;6323-6327, 2003 
    3. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T: Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity and transplantation tolerance. Immunol Rev 182;18-32, 2001 
    4. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S: Stimulation of CD25( +)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3;135-142, 2002 
    5. Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4;330-336, 2003 
    6. Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA: A role for TGF-beta in the generation and expansion of CD4+ CD25+ regulatory T cells from human peripheral blood. J Immunol 166;7282-7289, 2001 
    7. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS: The American Rheumatology Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31;315-324, 1988 
    8. Morgan ME, Sutmuller RP, Witteveen HJ, van Duivenvoorde LM, Zanelli E, Melief CJ, Snijders A, Offringa R, de Vries RR, Toes RE: CD25 + cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum 48;1452-1460, 2003 
    9. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA: CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167;1245-1253, 2001 
    10. Nishimura E, Sakihama T, Setoguchi R, Tanaka K, Sakaguchi S: Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising Foxp3+CD25+CD4+ regulatory T cells. Int Immunol 16;1189-1201, 2004 
    11. Cao D, Malmstrom V, Baecher-Allan C, Hafler D, Klareskog L, Trollmo C: Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis. Eur J Immunol 33; 215-223, 2003 
    12. Feldmann M, Brennan FM, Maini RN: Rheumatoid arthritis. Cell 85;307-310, 1996 
    13. Zheng SG, Wang JH, Gray JD, Soucier H, Horwitz DA: Natural and induced CD4+CD25+ cells educate CD4+ CD25- cells to develop suppressive activity: the role of IL-2, TGF-beta and IL-10. J Immunol 172;5213-5221, 2004 
    14. Fu S, Zhang N, Yopp AC, Chen D, Mao M, Chen D, Zhang H, Ding Y, Bromberg JS: TGF-beta induces Foxp3 + T-regulatory cells from CD4 + CD25 - precursors. Am J Transplant 4;1614-1627, 2004 
    15. Ehrenstein MR, Evans JG, Singh A, Moore S, Warnes G, Isenberg DA, Mauri C: Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNF alpha therapy. J Exp Med 200;277-285, 2004 
    16. Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K, Ten S, Sanz M, Exley M, Wilson B, Porcelli S, Maclaren N: Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest 109;131-140, 2002 
    17. van Amelsfort JM, van Roon JA, Noordergraaf M, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS: Proinflammatory mediated-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum 56;710-713, 2007 
    18. Powrie F, Correa-Oliveira R, Mauze S, Coffman RL: Regulatory interactions between CD45RBhigh and CD45RBlow CD4 + T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med 179;589-600, 1994 
    19. Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI: Defective suppressor function in CD4+CD25+T-cells from patients with type 1 diabetes. Diabetes 54;92-99, 2005 
    20. Lamas M, Sanz E, Martin-Parras L, Espel E, Sperisen P, Collins M, Silva AG: Glucocorticoid hormones upregulate interleukin 2 receptor alpha gene expression. Cell Immunol 151;437-450, 1993 
    21. Wraith DC: Role of interleukin-l0 in the induction and function of natural and antigen-induced regulatory T cells. J Autoimmun 20;273-275, 2003 
    22. Suri-Payer E, Cantor H: Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells. J Autoimmun 16;311-323, 2001 
    23. Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, Ye J, Masteller EL, McDevitt H, Bonyhadi M, Bluestone JA: In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199;1455-1465, 2004 
    24. Shevach EM: CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2;389-400, 2002 
    25. O'Garra A, Vieira P: Regulatory T cells and mechanisms of immune system conrrol. Nat Med 10;801-805, 2004 
    26. Lawson CA, Brown AK, Bejarano V, Douglas SH, Burgoyne CH, Greenstein AS, Boylston AW, Emery P, Ponchel F, Isaacs JD: Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology 29; Epub ahead of print, 2006 
    27. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M: Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various auto-immune diseases. J Immunol 155;1151-1164, 1995 
    28. Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science 299;1057-1061, 2003 
    29. Hoffmann P, Eder R, Kunz-Schughart LA, Andreesen R, Edinger M: Large-scale in vitro expansion of polyclonal human CD4(+)CD25high regulatory T cells. Blood 104; 895-903, 2004 
    30. Takahashi T, Tagami T, Yamazaki S, Uede T, Shimizu J, Sakaguchi N, Mak TW, Sakaguchi S: Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 192;303-310, 2000 
    31. van Amelsfort JM, Jacobs KM, Bijlsma JW, Lafeber FP, Taams LS: CD4(+ )CD25(+) regulatory T cells in rheumatoid arthritis: differences in the presence, phenotype and function between peripheral blood and synovial fluid. Arthritis Rheum 50;2775-2785, 2004 
    32. Yudoh K, Matsuno H, Nakazawa F, Yonezawa T, Kimura T: Reduced expression of the regulatory CD4+ T cell subset is related to Th1/Th2 balance and disease severity in rheumatoid arthritis. Arthritis Rheum 43;617-627, 2000 

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기