Age-Related Alterations in Regulatory T Cells

Chapter
First Online:

Abstract

Age-associated impaired function of the immune system seems to be a major contributory factor to the increased frequency of morbidity and mortality. Ageing affects different immune cell types, including hematopoietic stem cells, lymphoid progenitors in the bone marrow and thymus, thymic stromal cells, mature lymphocytes in secondary lymphoid organs, and elements of the innate immune system. Importantly, significant alterations are seen in the T lymphocyte compartment. Age-related alterations are evident in all stages of the T cell development making them a significant element in immunosenescence. Recent studies showed that T regulatory cells, a subset of CD4+ T cells with immunoregulatory activities, are also affected by ageing. The age-related alterations of Tregs, mechanisms underlying Treg homeostasis, and functions in ageing are described in this chapter.

Keywords

Treg Cell Aged Mouse Young Counterpart Secondary Lymphoid Organ Peripheral Tolerance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Agius E, Lacy KE, Vukmanovic-Stejic M et al (2009) Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. J Exp Med 206(9):1929–1940PubMedCrossRefGoogle Scholar
  2. Ahmad A, Banerjee S, Wang Z et al (2009) Aging and inflammation: etiological culprits of cancer. Curr Aging Sci 2(3):174–186PubMedCrossRefGoogle Scholar
  3. Anisimov VN (2009) Carcinogenesis and aging 20 years after: escaping horizon. Mech Ageing Dev 130(1–2):105–121PubMedCrossRefGoogle Scholar
  4. Bayer AL, Lee JY, de la Barrera A et al (2008) A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells. J Immunol 181(1):225–234PubMedGoogle Scholar
  5. Burchill MA, Yang J, Vogtenhuber C et al (2007) IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol 178(1):280–290PubMedGoogle Scholar
  6. Cheng G, Yuan X, Tsai MS et al (2012) IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells. J Immunol 189(4):1780–1791PubMedCrossRefGoogle Scholar
  7. Chiu BC, Stolberg VR, Zhang H et al (2007) Increased Foxp3(+) Treg cell activity reduces dendritic cell co-stimulatory molecule expression in aged mice. Mech Ageing Dev 128(11–12):618–627PubMedCrossRefGoogle Scholar
  8. Chougnet CA, Tripathi P, Lages CS et al (2011) A major role for Bim in regulatory T cell homeostasis. J Immunol 186(1):156–163PubMedCrossRefGoogle Scholar
  9. Ginaldi L, De Martinis M, Monti D et al (2004) The immune system in the elderly: activation-induced and damage-induced apoptosis. Immunol Res 30(1):81–94PubMedCrossRefGoogle Scholar
  10. Hakim FT, Flomerfelt FA, Boyiadzis M et al (2004) Aging, immunity and cancer. Curr Opin Immunol 16(2):151–156PubMedCrossRefGoogle Scholar
  11. Hamilton A (1991) Trauma training. Nurs Times 87(2):42–44PubMedGoogle Scholar
  12. Han GM, Zhao B, Jeyaseelan S et al (2009) Age-associated parallel increase of Foxp3(+)CD4(+) regulatory and CD44(+)CD4(+) memory T cells in SJL/J mice. Cell Immunol 258(2):188–196PubMedCrossRefGoogle Scholar
  13. Hoffmann P, Boeld TJ, Eder R et al (2009) Loss of FOXP3 expression in natural human CD4+CD25+ regulatory T cells upon repetitive in vitro stimulation. Eur J Immunol 39(4):1088–1097PubMedCrossRefGoogle Scholar
  14. Hwang KA, Kim HR, Kang I (2009) Aging and human CD4(+) regulatory T cells. Mech Ageing Dev 130(8):509–517PubMedCrossRefGoogle Scholar
  15. Kapp JA (2008) Special regulatory T-cell review: suppressors regulated but unsuppressed. Immunology 123(1):28–32PubMedCrossRefGoogle Scholar
  16. Kortylewski M, Xin H, Kujawski M et al (2009) Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell 15(2):114–123PubMedCrossRefGoogle Scholar
  17. Kurtulus S, Tripathi P, Moreno-Fernandez ME et al (2011) Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim. J Immunol 186(10):5729–5737PubMedCrossRefGoogle Scholar
  18. La Franceschi S, Vecchia C (2001) Cancer epidemiology in the elderly. Crit Rev Oncol Hematol 39(3):219–226PubMedCrossRefGoogle Scholar
  19. Lages CS, Suffia I, Velilla PA et al (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181(3):1835–1848PubMedGoogle Scholar
  20. Linton PJ, Li SP, Zhang Y et al (2005) Intrinsic versus environmental influences on T-cell responses in aging. Immunol Rev 205:207–219PubMedCrossRefGoogle Scholar
  21. Lustgarten J, Dominguez AL, Thoman M (2004) Aged mice develop protective antitumor immune responses with appropriate costimulation. J Immunol 173(7):4510–4515PubMedGoogle Scholar
  22. Macdonald JB, Dueck AC, Gray RJ et al (2011) Malignant melanoma in the elderly: different regional disease and poorer prognosis. J Cancer 2:538–543PubMedCrossRefGoogle Scholar
  23. Nishioka T, Shimizu J, Iida R et al (2006) CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice. J Immunol 176(11):6586–6593PubMedGoogle Scholar
  24. Pawelec G (1999) Immunosenescence: impact in the young as well as the old? Mech Ageing Dev 108(1):1–7PubMedCrossRefGoogle Scholar
  25. Pawelec G, Koch S, Franceschi C et al (2006) Human immunosenescence: does it have an infectious component? Ann N Y Acad Sci 1067:56–65PubMedCrossRefGoogle Scholar
  26. Plackett TP, Boehmer ED, Faunce DE et al (2004) Aging and innate immune cells. J Leukoc Biol 76(2):291–299PubMedCrossRefGoogle Scholar
  27. Provinciali M, Smorlesi A (2005) Immunoprevention and immunotherapy of cancer in ageing. Cancer Immunol Immunother 54(2):93–106PubMedCrossRefGoogle Scholar
  28. Rosenkranz D, Weyer S, Tolosa E et al (2007) Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration. J Neuroimmunol 188(1–2):117–127PubMedCrossRefGoogle Scholar
  29. Sakaguchi S, Sakaguchi N, Asano M 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):1151–1164PubMedGoogle Scholar
  30. Sakaguchi S, Miyara M, Costantino CM et al (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10(7):490–500PubMedCrossRefGoogle Scholar
  31. Santiago AF, Alves AC, Oliveira RP et al (2011) Aging correlates with reduction in regulatory-type cytokines and T cells in the gut mucosa. Immunobiology 216(10):1085–1093PubMedCrossRefGoogle Scholar
  32. Sharma S, Dominguez AL, Lustgarten J (2006) High accumulation of T regulatory cells prevents the activation of immune responses in aged animals. J Immunol 177(12):8348–8355PubMedGoogle Scholar
  33. Simone R, Zicca A, Saverino D (2008) The frequency of regulatory CD3+CD8+CD28–CD25+ T lymphocytes in human peripheral blood increases with age. J Leukoc Biol 84(6):1454–1461PubMedCrossRefGoogle Scholar
  34. Sun L, Hurez VJ, Thibodeaux SR et al (2012) Aged regulatory T cells protect from autoimmune inflammation despite reduced STAT3 activation and decreased constraint of IL-17 producing T cells. Aging Cell 11(3):509–519PubMedCrossRefGoogle Scholar
  35. Suzuki M, Jagger AL, Konya C et al (2012) CD8+CD45RA+CCR7+FOXP3+ T cells with immunosuppressive properties: a novel subset of inducible human regulatory T cells. J Immunol 189(5):2118–2130PubMedCrossRefGoogle Scholar
  36. Tan W, Zhang W, Strasner A et al (2011) Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 470(7335):548–553PubMedCrossRefGoogle Scholar
  37. Tang Q, Bluestone JA (2008) The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 9(3):239–244PubMedCrossRefGoogle Scholar
  38. Thornton AM, Korty PE, Tran DQ et al (2010) Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol 184(7):3433–3441PubMedCrossRefGoogle Scholar
  39. Todo-Bom A, Mota-Pinto A, Alves V et al (2012) Aging and asthma – changes in CD45RA, CD29 and CD95 T cells subsets. Allergol Immunopathol (Madr) 40(1):14–19CrossRefGoogle Scholar
  40. Trzonkowski P, Szmit E, Mysliwska J 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):307–316PubMedCrossRefGoogle Scholar
  41. Vigouroux S, Yvon E, Biagi E et al (2004) Antigen-induced regulatory T cells. Blood 104(1):26–33PubMedCrossRefGoogle Scholar
  42. Vukmanovic-Stejic M, Zhang Y, Cook JE 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):2423–2433PubMedCrossRefGoogle Scholar
  43. Wang L, Pan XD, Xie Y et al (2010) Altered CD28 and CD95 mRNA expression in peripheral blood mononuclear cells from elderly patients with primary non-small cell lung cancer. Chin Med J (Engl) 123(1):51–56Google Scholar
  44. Williams-Bey Y, Jiang J, Murasko DM (2011) Expansion of regulatory T cells in aged mice following influenza infection. Mech Ageing Dev 132(4):163–170PubMedCrossRefGoogle Scholar
  45. Wojciechowski S, Tripathi P, Bourdeau T et al (2007) Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med 204(7):1665–1675PubMedGoogle Scholar
  46. Zhao L, Sun L, Wang H et al (2007) Changes of CD4+CD25+Foxp3+ regulatory T cells in aged Balb/c mice. J Leukoc Biol 81(6):1386–1394PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyMcGill UniversityMontrealCanada
  2. 2.Meakins-Christie LaboratoriesMcGill UniversityMontrealCanada

Personalised recommendations