The role of naturally occurring regulatory CD4 +CD25 + T-cell subpopulation in the normal state and in various diseases



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Naturally occurring regulatory CD4 +CD25 + T cells (Treg cells) play a crucial role in the maintenance of normal immunohomeostasis.T reg cells suppress the activity of effector T cells thus taking part in the prevention of the development of autoimmune processes, whereas the inhibition of Treg cells activity can lead to the manifestation of severe or even fatal autoimmune and lymphoproliferative diseases. It has been shown that CD4 +CD25 +Treg cells play an important role in the suppression of graft-versus-host reaction, in the prevention of the development of allergic disorders and in the suppression of immune response to opportunistic pathogens. In patients with malignant neoplasms T reg cells inhibit the productive immune response against tumor.

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O V Akinfleva

Email: olgaakinf@yandex.ru

L N Bubnova

References

  1. Быковская С.Н., Насонов Е.Л. Роль дефектов иммуносупрессии в развитии аутоиммунных заболеваний // Науч. практ. ревматол. 2005. № 4. С. 81-84.
  2. Воробьев А.А., Быковская С.Н., Пашков Е.П. и др. Роль клеток-регуляторов CD25+CD4+ в развитии хронических инфекционных заболеваний // Вести. РАМН. 2006. № 9-10. С. 24-29.
  3. Свиридова В.С., Кологривова Е.Н., Пронина Н.А. и др. Т-лимфоциты - ключевые иммунорегуляторные клетки // Бюл. сиб. мед. 2007. № 1. С. 83-88.
  4. Asano М., Toda М., Sakaguchi N. et al. Autoimmune disease as a consequence of developmental abnormality of a cell subpopulation // J. Exp. Med. 1996. Vol. 184. P. 387-396.
  5. Baecher-Allan C., Viglieta V, Hafler D.A. Human CD4+CD25+ regulatory T cells // Semin. Immunol. 2004. Vol. 16. P. 89-98.
  6. Belkaid Y., Piccirillo C.A., Mendez S., Shevach E.M., Sacks D.L. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity // Nature. 2002. Vol. 420. P. 502-507.
  7. Bemrett C.L., Brunlcow M.E., Ramsdell E A rare polyadenylation signal mutation of the FOXP3 gene (AAU- AAA-AAUGAA) leads to the IPEX syndrome // Im- munogenetics. 2001. Vol. 53. P. 435^139.
  8. Berger C.L., Tigelaar R., Cohen J. Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells//Blood. 2005. Vol. 105. P. 1640-1647.
  9. Beyer C.L., Kochanek M., Darabi K. Reduced frequences and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine // Blood. 2005. Vol. 106. P. 2018-2025.
  10. BoettlerT., Spangenberg H.C., Neumann-HaefelinC. T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection // J. Virol. 2005. Vol. 79. P. 7860-7867.
  11. Bopp T. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression // J. Exp. Med. 2007. Vol. 204. P. 1303-1310.
  12. Borsellino G. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression // Blood. 2007. Vol. 110. P. 1225- 1232.
  13. Cao X. Granzyme В and perforin are important for regulatory T cell-mediated suppression of tumor clearance // Immunity. 2007. Vol. 27. P. 635-646.
  14. Caramalho I., Lopex-Carvalho T., Ostler D. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide // J. Exp. Med. 2003. Vol. 197. P. 403^111.
  15. Chai J.G., Xue S.A., Coe D., Addey C., Bartok I., ScottD. Regulatory T cells by in vitro Foxp3 gene transfer, can induce transplantation tolerance // Transplantation. 2005. Vol. 79. R 1310-1316.
  16. Chatila T.A. Role of regulatory T cells in human diseases // J. Allergy. Clin. Immunol. 2005. Vol. 116. P. 949-959.
  17. Cohen J.L., Trenado A., Vasey D. et al. CD4(+)CD25(+) immunoregulatory T cells: new therapeutics for graft-versus-host disease // J. Exp. Med. 2002. Vol. 196. P. 401-406.
  18. Cupedo T., Nagasawa M., Weijer K. Development and activation of regulatory T cells in the human fetus // Eur. J. Immunol. 2005. Vol. 35. P. 389-390.
  19. Curiel T.J., Coukos G., Zou L. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced'survival // Nat. Med. 2004. Vol. 10. P. 942-949.
  20. Deaglio S. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression // J. Exp. Med. 2007. Vol. 204. P. 1257-1265.
  21. Dieckmann D., Plottner H., Dotterweich S. et al. Activated CD4+CD25+ T cells suppress antigen-specific CD4+ and CD8+ T cells but induce a suppressive phenotype only in CD4+ T cells // Immunology. 2005. Vol. 115. P. 305-314.
  22. Earle K.E., Tang Q., Zhou X. In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation // Clin. Immunol. 2005. Vol. 115. P. 3-9.
  23. Edinger M., Hoffmann P., Ermann J. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation // Nat. Med. 2003. Vol. 9. P. 1144-1150.
  24. Eggena M.P., Barugahare B., Jones N. Depletion of regulatory T cells in HIV infection is associated with immune activation // J. Immunol. 2005. Vol. 174. P. 4407-4414.
  25. Elpek K.G., Lacelle Ch., Singh N.P. et al. CD4+CD25+ T regulatory cells dominate multiple immune evasion mechanisms in early but not late phases of tumor development in a В cell lymphoma model // J. Immunol. 2007. Vol. 178. P. 6840-6848.
  26. Fallarino F. Modulation of tryptophan catabolism by regulatory T cells // Nat. Immunol. 2003. Vol. 4. P. 1206-1212.
  27. Fehervari Zoltan and Shimon Salcaguchi. CD4+Tregs and immune control // J. Clin. Invest. 2004. Vol. 114. № 9. P. 1209-1217.
  28. Fehervari Zoltan and Shimon Sakaguchi. Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells // Intern. Immunol. 2004. Vol. 16(12). P. 1769-1780.
  29. Fontenot J.D., Rasmussen J.P., Williams L.M. et al. Regulatory T cell lineage specification by the forldiead transcription factor Foxp3 // Science. 2003. Vol. 299. P. 1057-1061.
  30. Fontenot J.D., Rasmussen J.P., Williams L.M. et al. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3 // Immunity. 2005. Vol. 22. P. 329-341.
  31. Furuichi Y., Tolcuyama H., Ueha S. Depletion of CD25+CD4+ T cells (Tregs) enhances the HBV-spe- cific CD8+ T cell responce primed by DNA immunization // Wld. J. Gastroenterol. 2005. Vol. 11. P. 3772- 3777.
  32. Gambineri E., Torgerson T.R., Ochs H.D. Immune dys-regulation, 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. Vol. 15. P. 430-435.
  33. Gavin M.A., Rasmussen J.P., Fontenot J.D. et al. Foxp3-dependent programme of regulatory T-cell differentiation//Nature. 2007. Vol. 445. P. 771-775.
  34. Gavin M., Rudensky A. Control of immune homeostasis by naturally arising regulatory CD4+ T cells // Curr. Opin. Immunol. 2003. Vol. 15. P. 690-696.
  35. Gondek D.C., Lu L-F., Quezada S.A. et al. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism // J. Immunol. 2005. Vol. 174. P. 1783-1786.
  36. Heier I., Hofgaard P.O., Brandtzag P. et al. Depletion of CD25+CD4+ regulatory T cells inhibits local tumour growth in a mouse model of В cell lymphoma // Clin. Exp. Immunol. 2008. Vol. 152. P. 381-387.
  37. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3 // Science. 2003. Vol. 299. P. 1057-1061.
  38. Huang C.T. et al. Role of LAG-3 in regulatory T cells // Immunity 2004. Vol. 21. P. 503-513.
  39. Joetham A. Naturally occurring lung CD4(+)CD25(+) T cell regulation of ail-way allergic responses depends on IL-10 induction of TGF-beta // J. Immunol. 2007. Vol. 178. P. 1433-1442.
  40. Kelchtermans H., De Klerck B., Mitera T. Defective CD4+CD25+ regulatory T cell functioning in collagen-induced arthritis an important factor in pathogenesis, counter-regulated by endogenous IFN-gamma // Arthr. Res. Ther. 2005. Vol. 7. № 2. P. 402^115.
  41. Khattri R., Cox T., Yasayko S.A. et al. An essential role for Scurfin in CD25+CD4+ T regulatory cells // Nat. Immunol. 2003. Vol. 4. P. 337-342.
  42. Kohno T., Yamada Y., Akamatsu N. Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells // Cancer. Sci. 2005. Vol. 96. P. 527-533.
  43. Kojima H., Kaimo Y., Hase H. et al. CD4+CD25+ regulatory T cells attenuate the phosphatidylinositol 3-lci- nase/Alet pathway in antigen-primed immature CD 8+ CTLs during functional maturation // J. Immunol. 2005. Vol. 174. P. 5959-5967.
  44. Levings M.K., Roncarolo M.G. T-regulatory cells: a novel subset of CD4 T cells with immunoregulatory properties// J. Allergy. Clin. Immunol. 2000. Vol. 106. P. 109-112.
  45. Liang B. et al. Regulatory T cells inhibit dendritic cells by LAG-3 engagement of MHC class II // J. Immunol. 2008. Vol. 180. P.5916-5926.
  46. Lim. H.W., Hillsamer P., Banhem A.H. et al. Cutting edge: direct suppression of В cells by CD4+CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus // J. Exp. Med. 2005. Vol. 201. P. 127-137.
  47. Loser K. IL-10 controls ultraviolet-induced carcinogenesis in mice // J. Immunol. 2007. Vol. 179. P. 365-371.
  48. Lundgren A., Stromberg E., Sjorling A. Mucosal FOXP3-expressing CD4+CD25high regulatory T cells in Helicobacter pylori-infected patients // Infect, and Immunol. 2005. Vol. 73. P. 523-531.
  49. McGuirk R, Mills K.H. Pathogen-specific regulatory T cells provoke a shift in the Thl/Th2 paradigm in immunity to infectious diseases // Trends Immunol. 2002. Vol. 23. P. 450^155.
  50. Mellor A.L., Munn D.H. IDO expression by dendritic cells: tolerance and tryptophan catabolism // Nat. Rev. Immunol. 2004. Vol. 4. P 762-774.
  51. Monk C.R., Spachidou M., Rovis F. MRL/Mp CD4+ CD25- T cells show reduced sensitivity to suppression by CD4+ CD25+ regulatory T cells in vitro: a novel T cell regulation in systemic lupus erythematosis // Ar- thr. and Rheum. 2005. Vol. 52. P. 1180-1184.
  52. Netea M.G., Van der Meer J.W., Kullberg В.J. Toll-like receptors as an escape mechanism from the host defense //Trends. Microbiol. 2004. Vol. 12. P. 484-488.
  53. Nishikawa H., Kato T., Tawara I. et al. Definition of target antigens for naturally occurring CD4+CD25+ regulatory T cells // J. Exp. Med. 2005. Vol. 201 № 5. P 681-686.
  54. Nomura T., Sakaguchi S. Naturally arising CD25+CD4+ regulatory T cells in tumor immunity // Cum. Top. Microbiol. Immunol. 2005. Vol. 293. P. 287-302.
  55. Ou L.S., Goleva E., Hall С. T regulatory cells in atopic dermatitis and subversion of their activity by superantigens // J. Allergy. Clin. Immunol. 2004. Vol. 113. P 756-763.
  56. Ouldca M. Interplay between pathogenic Thl7 and regulatory T cells // Ann. Rheum. 2007. Vol. 66. P 87-90.
  57. Papiemik M., de Moraes M.L., Pontoux C. Regulatory CD4 T cells: expression of IL-2R, resistance to clonal deletion and IL-2 dependency // Int. Immunol. 1998. Vol. 10. P. 371-378.
  58. Paust S., Cantor H. Regulatory T cells and autoimmune disease // Immunol. Rev. 2005. Vol. 204. P. 195-207.
  59. Peng G., Guo Z., Kinawa Y. Toll-like receptor 8-medi- ated reversal of CD4+ regulatory T cell function // Science. 2005. Vol. 309. P. 1380-1384.
  60. Sakaguchi S. Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptors // J. Exp. Med. 2003. Vol. 197. P. 397-401.
  61. Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses // Annu. Rev. Immunol. 2004. Vol. 22. P. 531-562.
  62. Sakaguchi S., Sakaguchi N, Shimuzu J. Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance // Immunol. Rev. 2001. Vol. 182. P. 18-32.
  63. Sasaki Y., Sakai M., Miyazaki S. Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases // Mol. Hum. Reprod. 2004. Vol. 10. P. 347-353.
  64. Shevach E.M. CD4+CD25+ suppressor T cells: more questions than answers // Nat. Rev. Immunol. 2002. Vol. 2. P 389-400.
  65. Shevach E.M. From vanilla to 28 flavors: multiple varieties of T regulatory cells // Immunity. 2006. ѴЫ. 25. P. 195-201.
  66. Shi H.Z., Li S., Xie Z.F. Regulatory CD4+CD25+ T lymphocytes in peripheral blood from patients with atopic asthma // Clin. Immunol. 2004. ѴЫ. 113. P. 172- 178.
  67. Singh B., Read S., Asseman C. Control of intestinal inflammation by regulatory T cells // Immunol. Rev. 2001. Vol. 18. P. 190-200.
  68. Suciu-Foca N., Manavalan J.S., Scotto L. Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells review // Int. Immunophar- macol. 2005. Vol. 5. P.7-11.
  69. Takahashi T., Kuniyasu Y., Toda M. Immunologic selftolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive stat // Int. Immunol. 1998. Vol. 10. P. 1969-1980.
  70. Takahashi T., Tagami T., Yamazaki S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4 // J. Exp. Med. 2000. Vol. 192. P. 303-310.
  71. Thornton A.M., Shevach E.M. CD4+CD25+ immuno- regulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production // J. Exp. Med. 1998. Vol. 188. P. 287-296.
  72. Тока F.N., Suvas S., Rouse B.T. CD4+CD25+ T cells regulate vaccine-generated primary and memory CD8+ T-cell responses against herpes simplex virus type 1 // J. Virol. 2004. Vol. 78. P. 13082-13089.
  73. Tsunemi S., Iwasaki T., Imado T. Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients //AIDS. 2005. Vol. 19. P. 879- 886.
  74. Tzankov A., Meier C., Hirschmann P. et al. Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large В-cell lymphoma, follicular lymphoma and classical Hodgkin's lymphoma // Haematologica. 2008. 193. Vol. 93. № 2. P. 193-200.
  75. Vignali A.A.D., Collison L.W., Workman C.J. How regulatory T cells work // Nat. Rev. Immunol. 2008. Vol. 8. № 7. p. 523-532.
  76. Waldmann H., Graca L., Cobbold S. Regulatory T cells and organ transplantation // Semin. Immunol. 2004. Vol. 16. P. 119-126.
  77. Watanabe N., Wang Y.H., Lee H.K. Hassal's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus //Nature.'2005. Vol. 436. P. 1181-1185.
  78. Weiss L., Donkova-Petrini V, Caccavelli L. Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients // Blood. 2004. Vol. 104. P. 3249-3256.
  79. Woo E.I., Yeh H., Chu C.S. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation // J. Immunol. 2002. Vol. 168. P. 4272-4276.
  80. Workman C.J., Vignali D.A.A. Negative regulation of T cell homeostasis by LAG-3 // J. Immunol. 2004. Vol. 174. P. 688-695.
  81. Yang Z.-Z., Novak A.J., Ziesmer S.C. et al. Attenuation of CD8+ T-cell function by CD4+CD25+ regulatory T cells in В-cell non-Hodgkin's lymphoma // Cancer. Res. 2006. Vol. 66. № 20. P 10145-10152
  82. Yang Z.-Z., Novak A. J., Ziesmer S.C. et al. CD70+ non- Hodgkin lymphoma В cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25“ T cells // Blood. 2007. Vol. 100. P. 2537-2544.
  83. Zarek P.E. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells // Blood. 2008. Vol. 111. P.251-259.
  84. Zelenay S., Lopez-Carvalho T., Caramalho I. Foxp3+ CD25~ cD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion // Proc. Natl. Acad. Sci. USA. 2005. Vol. 102. P. 4091-4096.
  85. Zencluzeen A.C. CD4+CD25+ T regulatory cells in murine pregnancy// J. Reprod. Immunol. 2005. Vol. 102. P. 4091^1096.
  86. Zhao D.M., Thornton A.M., DiPaolo R.J. et al. Activated CD4+CD25+ T cells selectively kill В lymphocytes //Blood. 2006. Vol. 107. P. 3925-3932.
  87. Zheng S.G., Wang J.H., Gray J.D. Natural and induced CD4+CD25+ cells educate CD4+CD25" to develop suppressive activity: the role of IL-2, TGF-beta and IL-10 //J. Immunol. 2004. Vol. 172. P. 5213-5221.

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