Особенности Т- регуляторных клеток у больных системной красной волчанкой
Аннотация
Т-регуляторные (Т-рег) клетки – субпопуляция CD4+ лимфоцитов, поддерживающая аутотолерантность организма путем подавления активности аутореактивных лимфоцитов. Существует гипотеза, что дефекты функций или снижение количества Т-рег-клеток лежат в основе патогенеза ряда аутоиммунных заболеваний. В статье рассмотрены основные особенности фенотипа Т-рег-клеток. Обсуждаются количество Т-рег-клеток как в периферической крови, так и в пораженных органах при системной красной волчанке, а также динамика уровня и функциональных способностей различных субпопуляций Т-рег-клеток на фоне иммуносупрессивной терапии. Кроме того, представлены различные подходы к использованию Т-рег-лимфоцитов в терапии аутоиммунных заболеваний.
Об авторах
А. В. Торгашина
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой».
Россия
Россия
Анна Васильевна Торгашина.
115522, Москва, Каширское шоссе, 34А.
С. К. Соловьев
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой».
Россия
115522, Москва, Каширское шоссе, 34А.
Россия
115522, Москва, Каширское шоссе, 34А.
Литература
1. Fontenot JD, RudenskyAY. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005 Apr;6(4):331-7.
2. Sakaguchi S. Regulatory T cells: history and perspective. Methods Mol Biol. 2011; 707:3-17. doi: 10.1007/978-1-61737-979-6_1.
3. Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3+CD25+CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005 Mar 7;201(5):723-735.
4. Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressingIL-2 receptor alpha-chains (CD25). Breakdown of a single mechanismof self-tolerance causes various autoimmune diseases. J Immunol. 1995 Aug 1; 155(3):1151-64.
5. MiyaraM, YoshiokaY, Kitoh A, et al. Functional delineation and differentiation dynamics of human CD4_ T cells expressing the FoxP3 transcription factor. Immunity. 2009 Jun 19;30(6):899-911. doi: 10.1016/j.immuni.2009.03.019. Epub 2009 May 21.
6. Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003 Dec 15;198(12):1875-86.
7. Ramsdell F, Ziegler SF. FOXP3 and scurfy: how it all began. Nat Rev Immunol. 2014 May; 14(5):343-9. doi: 10.1038/nri3650. Epub 2014 Apr 11.
8. Kleinewietfeld M, Starke M, Di Mitri D, et al. CD49d provides access to «untouched» human Foxp3+ Treg free of contaminating effector cells. Blood. 2009 Jan 22;113(4):827- 36. doi: 10.1182/blood-2008-04-150524. Epub 2008 Oct 21.
9. Seddiki N, Santner-Nanan B, Martinson J, et al. 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):1693-700. Epub 2006 Jul 3.
10. Liu W, Putnam AL, Xu-Yu Z, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006 Jul 10; 203(7):1701-11. Epub 2006 Jul 3.
11. Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol. 2010 Dec;10(12): 849-59. doi: 10.1038/nri2889.
12. Miyara M, Yoshioka Y, Kitoh A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity. 2009 Jun 19;30(6):899-911. doi: 10.1016/j.immuni.2009.03.019. Epub 2009 May 21.
13. Groux H, O'Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997 Oct 16;389(6652):737-42.
14. Grossman WJ, Verbsky JW, Barchet W, et al. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity. 2004 Oct;21(4):589-601.
15. Lim HW, Hillsamer P, Banham AH, Kim CH. Cutting edge: direct suppression of B cells by CD4+CD25+ regulatory T cells. J Immunol. 2005 Oct 1;175(7):4180-3.
16. Насонов ЕЛ, Насонова ВА, редакторы. Ревматология: национальное руководство. Москва: ГЭОТАР-Медиа; 2008.
17. Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016 Nov 22; 12(12):716-730. doi: 10.1038/nrrheum.2016.186.
18. Lee HY, HongYK, Yun HJ, et al. Altered frequency andmigration capacity of CD4+CD25+ regulatory T cells insystemic lupus erythematosus. Rheumatology (Oxford). 2008 Jun;47(6):789-94. doi: 10.1093/rheumatology/ken108. Epub 2008 Apr 3.
19. Xing Q, Wang B, Su H, et al. Elevated Th17 cells areaccompanied by FoxP3+ Treg cells decrease in patients with lupus nephritis. Rheumatol Int. 2012 Apr;32(4):949-58. doi: 10.1007/s00296-010-1771-0. Epub 2011 Jan 18.
20. Lyssuk EY, Torgashina AV, Soloviev SK, et al. Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus. Adv Exp Med Biol. 2007;601:113-9.
21. Prado C, Gomez J, Lopez P, et al. Dexamethasone upregulates FOXP3 expression without increasing regulatory activity. Immunobiology. 2011 Mar;216(3):386-92. doi: 10.1016/j.imbio.2010.06.013. Epub 2010 Jul 27.
22. Tselios K, Sarantopoulos A, Gkougkourelas I, et al. Increase of peripheral T regulatory cells during remission induction with cyclophosphamide in active systemic lupus erythematosus. Int J Rheum Dis. 2014 Sep;17(7):790-5. doi: 10.1111/1756-185X.12500.
23. Ma L, Zhao P., Jiang Z, et al. Imbalance of different types of CD4+forkhead box protein 3 (FoxP3)+T cells in patients with newonset systemic lupus erythematosus. Clin Exp Immunol. 2013 Dec;174(3):345-55. doi: 10.1111/cei.12189.
24. Prete M, Leone P, Frassanito MA, et al. Belimumab restores Treg/Th17 balance in patients with refractory systemic lupus erythematosus. Lupus. 2018 Oct;27(12): 1926-1935. doi: 10.1177/0961203318797425. Epub 2018 Sep 4.
25. Yates J, Whittington A, Mitchell P, et al. Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis. Clin Exp Immunol. 2008 Jul;153(1):44-55. doi: 10.1111/j.1365-2249.2008.03665.x. Epub 2008 May 23.
26. Zhang B, Zhang X, Tang FL, et al. Clinical significance of increased CD4+CD25-Foxp3+ T cells in patients with new onset systemic lupus erythematosus. Ann Rheum Dis. 2008 Jul;67(7):1037-40. doi: 10.1136/ard.2007.083543. Epub 2008 Jan 16.
27. Azab NA, Bassyouni IH, Emad Y, et al. CD4+CD25+ regulatory T cells (TREG) in systemic lupus erythematosus(SLE) patients: the possible influence of treatment with corticosteroids. Clin Immunol. 2008 May;127(2): 151-7. doi: 10.1016/j.clim.2007.12.010. Epub 2008 Mar 4.
28. Yan B, Ye S, Chen G, et al. Dysfunctional CD4+, CD25+ -regulatory T cells in untreated active systemic lupuserythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis Rheum. 2008 Mar;58(3):801-12. doi: 10.1002/art.23268.
29. Bonelli M, Gö schl L. CD4+CD25–Foxp3+ T cells: a marker for lupus nephritis? Arthritis Res Ther. 2014;16(2):R104
30. Wang G, Lai FM. Urinary FOXP3 mRNA in patients with lupus nephritis-relation with disease activity and treatment response. Rheumatology (Oxford). 2009 Jul; 48(7):755-60. doi: 10.1093/rheumatology/kep074. Epub 2009 May 20.
31. Suen J, Chiang BL. CD4DFoxP3D regulatory T-cells in human systemic lupus erythematosus. J Formos Med Assoc. 2012 Sep;111(9):465-70. doi: 10.1016/j.jfma.2012.05.013. Epub 2012 Aug 28.
32. Yan B, Liu Y. The Nature of Increased Circulating CD4+CD25-Foxp3+ T Cells in Patients with Systemic Lupus Erythematosus: A Novel Hypothesis. Open Rheumatol J. 2009 Jun 9;3:22-4. doi: 10.2174/1874312900903010022.
33. Shakweer MM, Behairy M.Value of Foxp3 expressing T-regulatory cells in renal tissue in lupus nephritis; an immunohistochemical study. J Nephropathol. 2016 Jul; 5(3):105-10. doi: 10.15171/jnp.2016.19. Epub 2016 Jul 2.
34. Yamazaki T, Yang XO, Chung Y, et al. CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol. 2008 Dec 15;181(12):8391-401.
35. Nocentini G, Alunno A, Petrillo MG, et al. Expansion of regulatory GITR+CD25low/- CD4+ T cells in systemic lupus erythematosus patients. Arthritis Res Ther. 2014;16(2):R444.
36. Schmidt A, Rieger CC. Analysis of FOXP3+ regulatory T cellsubpopulations in peripheral bloodand tissue of patients with systemiclupus erythematosus. Immunol Res. 2017 Apr;65(2):551-563. doi: 10.1007/s12026-017-8904-4.
37. Pan X, Yuan X, Zheng Y, et al. Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus. PLoS One. 2014 Mar 31;9(3):e93324. doi: 10.1371/journal.pone.0093324. eCollection 2014.
38. Dolff S, Bijl M, Huitema MG, et al. Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus. Clin Immunol. 2011 Nov;141(2): 197-204. doi: 10.1016/j.clim.2011.08.005. Epub 2011 Aug 16.
39. Humrich JY, Morbach H, Undeutsch R, et al. Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):204-9. doi: 10.1073/pnas.0903158107. Epub 2009 Dec 14.
40. Bailey-Bucktrout SL, Martinez-Llordella M, Zhou X, et al. Self-antigen-Driven Activation Induces Instability of Regulatory T Cells during an Inflammatory Autoimmune Response. Immunity. 2013 Nov 14;39(5):949-62. doi: 10.1016/j.immuni.2013.10.016.
41. Nakamura K, Kitani A, Fuss I, et al. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol. 2004 Jan 15;172(2):834-42.
42. Goodman WA, Young AB, McCormick TS, et al. Stat3 phosphorylation mediates resistance of primary human T cells to regulatory T cell suppression. J Immunol. 2011 Mar 15;186(6):3336-45. doi: 10.4049/jimmunol.1001455. Epub 2011 Feb 9.
43. Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010 Jul;40(7):1830-5. doi: 10.1002/eji.201040391.
44. Yang XO, Nurieva R, Martinez GJ, et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity. 2008 Jul 18;29(1):44-56. doi: 10.1016/j.immuni.2008.05.007. Epub 2008 Jun 26.
45. Mao X, Wu Y, Diao H, et al. Interleukin-6 promotessystemic lupus erythematosus progression with Treg suppression approachin a murine systemic lupus erythematosus model. Clin Rheumatol. 2014 Nov;33(11):1585-93. doi: 10.1007/s10067-014-2717-9. Epub 2014 Jun 15.
46. Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol. 2014 Aug;35(3):347-69. doi: 10.1016/j.yfrne.2014.04.004. Epub 2014 May 2.
47. He J, Zhang X, Wei Y, et al. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus. Nat Med. 2016 Sep;22(9):991-3. doi: 10.1038/nm.4148. Epub 2016 Aug 8.
48. Mizui M, Tsokos GC. Targeting Regulatory T Cells to Treat Patients with Systemic Lupus erythematosus. Front Immunol. 2018 Apr 17;9:786. doi: 10.3389/fimmu.2018.00786. eCollection 2018.
49. Scalapino KJ, Tang Q, Bluestone JA, et al. Suppression of disease in New Zealand Black/New Zealand white lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells. J Immunol. 2006 Aug 1;177(3): 1451-9.
50. Weigert O, von Spee C, Undeutsch R, et al. CD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus mice. Arthritis Res Ther. 2013 Feb 27;15(1):R35. doi: 10.1186/ar4188.
51. Dai Z, Turtle CJ, Booth GC, et al . Normally occurring NKG2D+CD4+ T cells are immunosuppressive and inversely correlated with disease activity injuvenile-onset lupus. J Exp Med. 2009 Apr 13;206(4):793- 805. doi: 10.1084/jem.20081648. Epub 2009 Mar 16.
52. Golding A, Hasni S, Golding A, Hasni S. The Percentage of FoxP3+Helios+ Treg Cells Correlates Positively With Disease Activity in Systemic Lupus Erythematosus. Arthritis Rheum. 2013 Nov;65(11):2898-906. doi: 10.1002/art.38119.
53. Alexander T, Sattler A. Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus. Ann Rheum Dis. 2013 Sep 1;72(9):1549-58. doi: 10.1136/ annrheumdis-2012-202216. Epub 2012 Dec 21.
54. El-Maraghy N, Ghaly MS, Dessouki O, et al. CD4+CD25-Foxp3+ T cells as a marker of disease activity and organ damage in systemic lupus erythematosus patients. Arch Med Sci. 2018 Aug;14(5):1033-1040. doi: 10.5114/aoms.2016.63597. Epub 2016 Nov 15.
55. Zabinska M, Krajewska M, Koscielska- Kasprzak K, et al. CD4+CD25+CD1272 and CD4+CD25+Foxp3+ Regulatory T Cell Subsets in Mediating Autoimmune Reactivity in Systemic Lupus Erythematosus Patients. Arch Immunol Ther Exp (Warsz). 2016 Oct; 64(5):399-407. doi: 10.1007/s00005-016-0399-5. Epub 2016 May 7.
56. Vitales-Noyola M, Oceguera-Maldonado B, Nino-Moreno P, et al. Patients with Systemic Lupus Erythematosus Show Increased Levels and Defective Function of CD69+ T Regulatory Cells. Mediators Inflamm. 2017;2017:2513829. doi: 10.1155/2017/2513829. Epub 2017 Sep 6.
57. Silva-Neta HL, Brelaz-de-Castro MCA, Chagas MBO, et al. CD4+CD45RAFOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients. Biomed Res Int. 2018 Jun 12;2018:3419565. doi: 10.1155/2018/3419565. eCollection 2018.
Для цитирования:
Торгашина А.В., Соловьев С.К. Особенности Т- регуляторных клеток у больных системной красной волчанкой. Современная ревматология. 2018;12(4):9-15. https://doi.org/10.14412/1996-7012-2018-4-9-15
For citation:
Torgashina A.V., Solovyev S.К. Specific features of regulatory T cells in patients with systemic lupus erythematosus. Modern Rheumatology Journal. 2018;12(4):9-15. (In Russ.) https://doi.org/10.14412/1996-7012-2018-4-9-15
Просмотров: 324
Послать статью по эл. почте 