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The Role of T-regulatory Cells in Immune Senescence

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Handbook on Immunosenescence

T-regulatory cells have come to dominate immunology over the last decade [1]. The ability of cellular components of the immune system to suppress immune function was noticed more than 20 years ago and was recognized by a number of highly cited publications [2]. However, the lack of a specific phenotype for these cells, and an inability to document precise physiological mechanisms for their action, limited their investigation by detailed experimental study. The pioneering work of Sakaguchi and colleagues reestablished regulatory cells and has generated a field of research that extends into all areas of clinical immunology, including immune senescence [3].

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References

  1. Banham AH, FM Powrie, E Suri-Payer (2006) FOXP3+ regulatory T-cells: current controversies and future perspectives. Eur J Immunol 36 (11):p. 2832–2836

    Article  PubMed  CAS  Google Scholar 

  2. Dorf ME, B Benacerraf (1984) Suppressor cells and immuno-regulation. Annu Rev Immunol 2 :p. 127–157

    Article  PubMed  CAS  Google Scholar 

  3. Sakaguchi S, et al (1995) 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 155 (3):p. 1151–1164

    PubMed  CAS  Google Scholar 

  4. Hori S, T Nomura, S Sakaguchi (2003) Control of regulatory T-cell development by the transcription factor Foxp3 . Science 299 (5609):p. 1057–1061

    Article  PubMed  CAS  Google Scholar 

  5. Fontenot JD, MA Gavin, AY Rudensky (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T-cells. Nat Immunol 4 (4):p. 330–336

    Article  PubMed  CAS  Google Scholar 

  6. Seddiki N, et al (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T-cells . J Exp Med 203 (7):p. 1693–1700

    Article  PubMed  CAS  Google Scholar 

  7. Liu W, et al (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4 +T-reg cells. J Exp Med 203 (7):p. 1701–1711

    Article  PubMed  CAS  Google Scholar 

  8. Borsellino G, et al (2007) Expression of ectonucleotidase CD39 by Foxp3+ Treg-cells: hydrolysis of extracellular ATP and immune suppression . Blood 110 (4):p. 1225–1232

    Article  PubMed  CAS  Google Scholar 

  9. Walker MR, et al (2003) Induction of FoxP3 and acquisition of T-regulatory activity by stimulated human CD4+CD25- T-cells. J Clin Invest 112 (9):p. 1437–1443

    PubMed  CAS  Google Scholar 

  10. Zheng SG, et al (2004) 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 (9):p.

    PubMed  CAS  Google Scholar 

  11. Selvaraj RK, TL Geiger (2007) A kinetic and dynamic analysis of Foxp3 induced in T cells by TGF-beta. J Immunol 179 (2):p. 11 following 1390 5213–5221

    Google Scholar 

  12. Vukmanovic-Stejic M, et al (2006) Human CD4+ CD25hi Foxp3+ regulatory T-cells are derived by rapid turnover of memory populations in vivo . J Clin Invest 116 (9):p. 2423–2433

    Article  PubMed  CAS  Google Scholar 

  13. Blais ME, et al (2008) Why T-cells of thymic versus extrathymic origin are functionally different. J Immunol 180 (4):p. 2299–2312

    PubMed  CAS  Google Scholar 

  14. Kim JM, JP Rasmussen, AY Rudensky (2007) Regulatory T-cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8 (2):p. 191–197

    Article  PubMed  CAS  Google Scholar 

  15. Zhao L, et al (2007) Changes of CD4+CD25+Foxp3+ regulatory T-cells in aged Balb/c mice. J Leukoc Biol 81 (6):p. 1386–1394

    Article  PubMed  CAS  Google Scholar 

  16. Kozlowska E, et al (2007) Age-related changes in the occurrence and characteristics of thymic CD4(+) CD25(+) T-cells in mice. Immunology 122 (3):p. 445–453

    Article  PubMed  CAS  Google Scholar 

  17. Nishioka T, et al (2006) CD4+CD25+Foxp3+ T-cells and CD4+CD25-Foxp3+ T-cells in aged mice. J Immunol 176 (11):p. 6586–6593

    PubMed  CAS  Google Scholar 

  18. Shimizu J, E Moriizumi (2003) CD4+CD25- T-cells in aged mice are hyporesponsive and exhibit suppressive activity. J Immunol 170 (4):p. 1675–1682

    PubMed  CAS  Google Scholar 

  19. Gregg R, et al (2005) The number of human peripheral blood CD4+ CD25high regulatory Tcells increases with age . Clin Exp Immunol 140 (3):p. 540–546

    Article  PubMed  CAS  Google Scholar 

  20. Bryl E, JM Witkowski (2004) Decreased proliferative capability of CD4(+) cells of elderly people is associated with faster loss of activation-related antigens and accumulation of regulatory T-cells . Exp Gerontol 39 (4):p. 587–595

    Article  PubMed  CAS  Google Scholar 

  21. Trzonkowski P, et al (2006) CD4+CD25+ T-regulatory cells inhibit cytotoxic activity of CTL and NK-cells in humans-impact of immunosenescence. Clin Immunol 119 (3):p. 307–316

    Article  PubMed  CAS  Google Scholar 

  22. Rosenkranz D, et al (2007) Higher frequency of regulatory T-cells in the elderly and increased suppressive activity in neurodegeneration. J Neuroimmunol 188 (1–2):p. 117–127

    Article  PubMed  CAS  Google Scholar 

  23. Tsaknaridis L, et al (2003) Functional assay for human CD4+CD25+ Treg-cells reveals an age-dependent loss of suppressive activity. J Neurosci Res 74 (2):p. 296–308

    Article  PubMed  CAS  Google Scholar 

  24. Agrawal A, et al (2007) Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178 (11):p. 6912–6922

    PubMed  CAS  Google Scholar 

  25. Seddiki N, et al (2006) Persistence of naive CD45RA+ regulatory T-cells in adult life. Blood 107 (7):p. 2830–2838

    Article  PubMed  CAS  Google Scholar 

  26. Czesnikiewicz-Guzik M, et al (2008) T-cell subset-specific susceptibility to aging. Clin Immunol

    Google Scholar 

  27. Allan SE, et al (2007) Activation-induced FOXP3 in human T-effector cells does not suppress proliferation or cytokine production. Int Immunol 19 (4):p. 345–354

    Article  PubMed  CAS  Google Scholar 

  28. Kiniwa Y, et al (2007) CD8+ Foxp3+ regulatory T-cells mediate immuno-suppression in prostate cancer. Clin Cancer Res 13 (23):p. 6947–6958

    Article  PubMed  CAS  Google Scholar 

  29. Meloni F, et al (2006) Foxp3 expressing CD4+ CD25+ and CD8+CD28- T-regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma. Hum Immunol 67 (1–2):p. 1–12

    Article  PubMed  CAS  Google Scholar 

  30. Pacholczyk R, et al (2006) Origin and T-cell receptor diversity of Foxp3+CD4+CD25+ T-cells. Immunity 25 (2):p. 249–259

    Article  PubMed  CAS  Google Scholar 

  31. Hsieh CS, et al (2006) An intersection between the self-reactive regulatory and nonregulatory T-cell receptor repertoires. Nat Immunol 7 (4):p. 401–410

    Article  PubMed  CAS  Google Scholar 

  32. Rudge G, et al (2007) Infiltration of a mesothelioma by IFN-gamma-producing cells and tumor rejection after depletion of regulatory T-cells. J Immunol 178 (7):p. 4089–4096

    PubMed  CAS  Google Scholar 

  33. Chaput N, et al (2007) Regulatory T-cells prevent CD8 T-cell maturation by inhibiting CD4 Th-cells at tumor sites. J Immunol 179 (8):p. 4969–4978

    PubMed  CAS  Google Scholar 

  34. Hodi FS, et al (2008) Immunologic and clinical effects of antibody blockade of cytotoxic T-lymphocyte-associated antigen-4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A

    Google Scholar 

  35. Dejaco C, C Duftner, M Schirmer (2006) Are regulatory T-cells linked with aging? Exp Gerontol 41 (4):p. 339–345

    Article  PubMed  CAS  Google Scholar 

  36. Sharma S, AL Dominguez, J Lustgarten (2006) High accumulation of T-regulatory cells prevents the activation of immune responses in aged animals. J Immunol 177 (12):p. 8348–8355

    PubMed  CAS  Google Scholar 

  37. Aspinall R (2006) T-cell development, ageing and Interleukin-7. Mech Ageing Dev 127 (6):p. 572–578

    Article  PubMed  CAS  Google Scholar 

  38. Kared H, et al (2005) Treatment with granulocyte colony-stimulating factor prevents diabetes in NOD mice by recruiting plasmacytoid dendritic cells and functional CD4(+)CD25(+) regulatory T-cells. Diabetes 54 (1):p. 78–84

    Article  PubMed  CAS  Google Scholar 

  39. Pesic V, et al (2007) Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. Int Immunopharmacol 7 (5):p. 674–686

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TT, Birmingham, UK

    Paul Moss

Authors
  1. Paul Moss
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Editor information

Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

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Moss, P. (2009). The Role of T-regulatory Cells in Immune Senescence. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_10

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