medigraphic.com
ISSN 0016-3813 (Print)

2013, Number 6

<< Back Next >>

Gac Med Mex 2013; 149 (6)

Mechanisms of suppression of regulatory T-cells (Treg)

Guzmán-Flores JM, Portales-Pérez DP

Language: Spanish
References: 69
Page: 630-638
PDF size: 267.57 Kb.


ABSTRACT

An important feature of immunology is understanding how the immune system is able to discriminate between self and non-self. Regulatory T-cells (Treg) actively inhibit immune responses involved in the pathological and physiological responses, and, in consequence, contribute to the maintenance of homeostasis. The characterization of these regulatory T-cells has been controversial due to the lack of exclusive markers for their identification and isolation. The mechanisms that regulatory T-cells use to function are: cytokines, death cells, modullation of the microenvironment, and surface receptors. The immune system and Treg cells have been related to obesity and type 2 diabetes mellitus through the inflammatory process. In this work, we review the proposed markers for Treg cells, recent data on the mechanism used for the main function of Treg cells, immune regulation, and we conclude with the impact of these cells on obesity and type 2 diabetes mellitus.


REFERENCES

  1. Yamaguchi T, Wing JB, Sakaguchi S. Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions. Semin Immunol. 2011;23(6):424-30.

  2. 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 autoimmune diseases. J Immunol. 1995;155(3): 1151-64.

  3. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057-61.

  4. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4(4):330-6.

  5. Allan SE, Crome SQ, Crellin NK, et al. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol. 2007;19(4):345-54.

  6. Thornton AM, Korty PE, Tran DQ, et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol. 2010;184(7):3433-41.

  7. Schmetterer KG, Neunkirchner A, Pickl WF. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J. 2012;26(6):2253-76.

  8. Yi H, Zhen Y, Jiang L, Zheng J, Zhao Y. The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells. Cell Mol Immunol. 2006;3(3):189-95.

  9. Chen X, Oppenheim JJ. Resolving the identity myth: key markers of functional CD4+FoxP3+ regulatory T cells. Int Immunopharmacol. 2011;11(10):1489-96.

  10. Shevach EM. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity. 2006;25(2):195-201.

  11. Peterson RA. Regulatory T-cells: diverse phenotypes integral to immune homeostasis and suppression. Toxicol Pathol. 2012;40(2):186-204.

  12. Workman CJ, Szymczak-Workman AL, Collison LW, Pillai MR, Vignali DA. The development and function of regulatory T cells. Cell Mol Life Sci. 2009;66(16):2603-22. Gaceta Médica de México. 2013;149 638

  13. Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 2007;13(3):108-16.

  14. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8(12):1353-62.

  15. Oberle N, Eberhardt N, Falk CS, Krammer PH, Suri-Payer E. Rapid suppression of cytokine transcription in human CD4+CD25 T cells by CD4+Foxp3+ regulatory T cells: independence of IL-2 consumption, TGF-beta, and various inhibitors of TCR signaling. J Immunol. 2007;179(6):3578-87.

  16. Collison LW, Pillai MR, Chaturvedi V, Vignali DA. 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):6121-8.

  17. Fassbender M, Gerlitzki B, Ullrich N, et al. Cyclic adenosine monophosphate and IL-10 coordinately contribute to nTreg cell-mediated suppression of dendritic cell activation. Cell Immunol. 2010;265(2):91-6.

  18. Taams LS, Smith J, Rustin MH, Salmon M, Poulter LW, Akbar AN. Human anergic/suppressive CD4(+)CD25(+) T cells: a highly differentiated and apoptosis-prone population. Eur J Immunol. 2001;31(4):1122-31.

  19. Green EA, Gorelik L, McGregor CM, Tran EH, Flavell RA. CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGFbeta receptor interactions in type 1 diabetes. Proc Natl Acad Sci U S A. 2003;100(19):10878-83.

  20. Piccirillo CA, Letterio JJ, Thornton AM, et al. CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med. 2002;196(2):237-46.

  21. 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;198(12):1875-86.

  22. Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007;450 (7169):566-9.

  23. Collison LW, Chaturvedi V, Henderson AL, et al. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 2010;11(12):1093-101.

  24. Bardel E, Larousserie F, Charlot-Rabiega P, Coulomb-L’Hermine A, Devergne O. Human CD4+ CD25+ Foxp3+ regulatory T cells do not constitutively express IL-35. J Immunol. 2008;181(10):6898-905.

  25. Chaturvedi V, Collison LW, Guy CS, Workman CJ, Vignali DA. Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J Immunol. 2011;186(12):6661-6.

  26. Lu LF, Lind EF, Gondek DC, et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature. 2006;442(7106):997-1002.

  27. Putheti P, Awasthi A, Popoola J, Gao W, Strom TB. Human CD4 memory T cells can become CD4+IL-9+ T cells. PLoS One. 2010;5(1): e8706.

  28. Elyaman W, Bradshaw EM, Uyttenhove C, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci U S A. 2009;106(31):12885-90.

  29. Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol. 2005;174(4):1783-6.

  30. Zhao DM, Thornton AM, DiPaolo RJ, Shevach EM. Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood. 2006;107(10):3925-32.

  31. Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27(4):635-46.

  32. Ren X, Ye F, Jiang Z, Chu Y, Xiong S, Wang Y. Involvement of cellular death in TRAIL/DR5-dependent suppression induced by CD4(+)CD25(+) regulatory T cells. Cell Death Differ. 2007;14(12):2076-84.

  33. Strauss L, Bergmann C, Whiteside TL. Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis. J Immunol. 2009;182(3):1469-80.

  34. Cedeno-Laurent F, Dimitroff CJ. Galectin-1 research in T cell immunity: past, present and future. Clin Immunol. 2012;142(2):107-16.

  35. Garin MI, Chu CC, Golshayan D, Cernuda-Morollon E, Wait R, Lechler RI. Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood. 2007;109(5):2058-65.

  36. Kubach J, Lutter P, Bopp T, et al. Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood. 2007;110(5):1550-8.

  37. McHugh RS, Whitters MJ, Piccirillo CA, et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity. 2002;16(2):311-23.

  38. Szymczak-Workman AL, Delgoffe GM, Green DR, Vignali DA. Cutting edge: regulatory T cells do not mediate suppression via programmed cell death pathways. J Immunol. 2011;187(9):4416-20.

  39. Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204(6):1257-65.

  40. Hasko G, Kuhel DG, Chen JF, et al. Adenosine inhibits IL-12 and TNF- [alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J. 2000;14(13):2065-74.

  41. Nemeth ZH, Lutz CS, Csoka B, et al. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. J Immunol. 2005;175(12):8260-70.

  42. Bopp T, Becker C, Klein M, et al. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J Exp Med. 2007;204(6):1303-10.

  43. Yan Z, Garg SK, Kipnis J, Banerjee R. Extracellular redox modulation by regulatory T cells. Nat Chem Biol. 2009;5(10):721-3.

  44. Efimova O, Szankasi P, Kelley TW. Ncf1 (p47phox) is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells. PLoS One. 2011;6(1):e16013.

  45. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322(5899):271-5.

  46. Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A. 2008;105(29):10113-8.

  47. Paust S, Lu L, McCarty N, Cantor H. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci U S A. 2004;101(28):10398-403.

  48. Okamura T, Fujio K, Sumitomo S, Yamamoto K. Roles of LAG3 and EGR2 in regulatory T cells. Ann Rheum Dis. 2012;71 Suppl 2:i96-100.

  49. Liang B, Workman C, Lee J, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J Immunol. 2008;180(9):5916-26.

  50. Huang CT, Workman CJ, Flies D, et al. Role of LAG-3 in regulatory T cells. Immunity. 2004;21(4):503-13.

  51. Camisaschi C, Casati C, Rini F, et al. LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites. J Immunol. 2010;184(11):6545-51.

  52. Reinwald S, Wiethe C, Westendorf AM, et al. CD83 expression in CD4+ T cells modulates inflammation and autoimmunity. J Immunol. 2008;180(9):5890-7.

  53. Garcia-Hernandez MH, Alvarado-Sanchez B, Calvo-Turrubiartes MZ, et al. Regulatory T Cells in children with intestinal parasite infection. Parasite Immunol. 2009;31(10):597-603.

  54. Guzman-Flores JM, Lopez-Briones S. Cells of innate and adaptive immunity in type 2 diabetes and obesity. Gac Med Mex. 2012;148(4):381-9.

  55. Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol. 2012;8(12):709-16.

  56. Deiuliis J, Shah Z, Shah N, et al. Visceral adipose inflammation in obesity is associated with critical alterations in tregulatory cell numbers. PLoS One. 2011;6(1):e16376.

  57. Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15(8):930-9.

  58. Defuria J, Belkina AC, Jagannathan-Bogdan M, et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A. 2013;110(13):5133-8.

  59. Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A. Regulatory T cells in obesity: the leptin connection. Trends Mol Med. 2010;16(6):247-56.

  60. Zeyda M, Huber J, Prager G, Stulnig TM. Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity (Silver Spring). 2011;19(4):743-8.

  61. van der Weerd K, Dik WA, Schrijver B, et al. Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype. Diabetes. 2012;61(2):401-8.

  62. Svec P, Vasarhelyi B, Paszthy B, et al. Do regulatory T cells contribute to Th1 skewness in obesity? Exp Clin Endocrinol Diabetes. 2007; 115(7):439-43.

  63. Jagannathan-Bogdan M, McDonnell ME, Shin H, et al. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J Immunol. 2011;186(2):1162-72.

  64. Zeng C, Shi X, Zhang B, et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. J Mol Med (Berl). 2012;90(2):175-86.

  65. Winer S, Chan Y, Paltser G, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 2009;15(8): 921-9.

  66. Eller K, Kirsch A, Wolf AM, et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes. 2011;60(11):2954-62.

  67. Ilan Y, Maron R, Tukpah AM, et al. Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. Proc Natl Acad Sci U S A. 2010;107(21):9765-70.

  68. Tian J, Dang HN, Yong J, et al. Oral treatment with gamma-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. PLoS One. 2011;6(9):e25338.

  69. Yun JM, Jialal I, Devaraj S. Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers. Br J Nutr. 2010;103(12):1771-7.




2020     |     www.medigraphic.com