Skip to main content

Advertisement

Log in

Impaired CD4+CD25+ regulatory T cell activity in the peripheral blood of patients with autoimmune sensorineural hearing loss

  • Otology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

CD4+CD25+ regulatory T cells exert an immune regulatory function and thus play an important role in the control of self-reactivity in the pathogenesis of autoimmune inflammatory conditions. The aim of the study presented here is to perform a quantitative and functional analyses of these cells in patients with autoimmune sensorineural hearing loss (ASNHL). T cell subsets (CD4+CD25+, CD4+CD25high, CD4+, and CD8+) from the peripheral blood of 17 patients with ASNHL, 16 patients with noise induced hearing loss (NHL), and 100 normal controls were analyzed by flow cytometry. The CD4/CD8 ratio was also analyzed. In addition, the suppressive capability of CD4+CD25+ T cells was tested in vitro by measuring their ability to suppress the proliferation and IFN-γ secretion of CD4+CD25 T cells. No significant difference was found in the T cell subsets of ASNHL patients compared to normal controls or NHL patients, except that the proportion of CD4+ T cells was elevated in ASNHL patients. However, we did observe defective regulatory function of CD4+CD25+T cells in patients with ASNHL. Our data supported the idea that CD4+CD25+ regulatory T cells played an immunosuppressive function in the periphery. The impaired suppressive activity of these cells may be an important factor in the pathogenesis of ASNHL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. McCabe BF (1979) Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol 88:585–589

    PubMed  CAS  Google Scholar 

  2. Solares CA, Hughes GB, Tuohy VK (2003) Autoimmune sensorineural hearing loss: an immunologic perspective. J Neuroimmunol 138:1–7

    Article  PubMed  CAS  Google Scholar 

  3. McCabe BF, McCormick KJ (1984) Tests for autoimmune disease in otology. Am J Otol 5:447–449

    PubMed  CAS  Google Scholar 

  4. Lorenz RR, Solares CA, Williams P, Sikora J, Pelfrey CM, Hughes GB, Tuohy VK (2002) Interferon-gamma production to inner ear antigens by T cells from patients with autoimmune sensorineural hearing loss. J Neuroimmunol 130:173–178

    Article  PubMed  CAS  Google Scholar 

  5. Yamanobe S, Harris JP (1992) Spontaneous remission in experimental autoimmune labyrinthitis. Ann Otol Rhinol Laryngol 101:1007–1014

    PubMed  CAS  Google Scholar 

  6. Gloddek B, Gloddek J, Arnold W (1999) A rat T-cell line that mediates autoimmune disease of the inner ear in the Lewis rat. ORL J Otorhinolaryngol Relat Spec 61:181–187

    PubMed  CAS  Google Scholar 

  7. Ito Y, Nieda M, Uchigata Y, Nishimura M, Tokunaga K, Kuwata S et al (1993) Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors. J Immunol 151:5770–5776

    PubMed  CAS  Google Scholar 

  8. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA (1990) T-cell recognition of an immunodominant myelin basic protein epitope inmultiple sclerosis. Nature 346:183–187

    Article  PubMed  CAS  Google Scholar 

  9. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (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 155:1151–1164

    PubMed  CAS  Google Scholar 

  10. O’Garra A, Vieira P (2004) Regulatory T cells and mechanisms of immune system control. Nat Med 10:801–805

    Article  PubMed  CAS  Google Scholar 

  11. Li Z, Mahesh SP, Kim BJ, Buggage RR, Nussenblatt RB (2003) Expression of glucocorticoid induced TNF receptor family related protein (GITR) on peripheral T cells from normal human donors and patients with non-infectious uveitis. J Autoimmun 21:83–92

    Article  PubMed  CAS  Google Scholar 

  12. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25+ high regulatory cells in human peripheral blood. J Immunol 167:1245–1253

    PubMed  CAS  Google Scholar 

  13. Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH (2001) Identification and functional characterization of human CD4 (+)CD25 (+) T cells with regulatory properties isolated from peripheral blood. J Exp Med 193:1285–1294

    Article  PubMed  CAS  Google Scholar 

  14. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199:971–979

    Article  PubMed  CAS  Google Scholar 

  15. Cao D, Malmstrom V, Baecher-Allan C, Hafler D, Klareskog L, Trollmo C (2003) Isolation and functional characterization of regulatory CD25 bright CD4+ T cells from the target organ of patients with rheumatoid arthritis. Eur J Immunol 33:215–223

    Article  PubMed  CAS  Google Scholar 

  16. Kukreja A, Cost G, Marker J, Zhang C, Sun Z, Lin-Su K et al (2002) Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest 109:131–140

    PubMed  CAS  Google Scholar 

  17. Harris JP, Weisman MH, Derebery JM, Espeland MA, Gantz BJ, Gulya AJ et al (2003) Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA 290:1875–1883

    Article  PubMed  CAS  Google Scholar 

  18. Baek MJ, Park HM, Johnson JM, Altuntas CZ, Jane-Wit D, Jaini R et al (2006) Increased frequencies of cochlin-specific t cells in patients with autoimmune sensorineural hearing loss. J Immunol 177:4203–4210

    PubMed  CAS  Google Scholar 

  19. Cao D, van Vollenhoven R, Klareskog L, Trollmo C, Malmström V (2004) CD25 bright CD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis Res Ther 6:335–346

    Article  Google Scholar 

  20. Jiang S, Camara N, Lombardi G, Lechler RI (2003) Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex-vivo. Blood 102:2180–2186

    Article  PubMed  CAS  Google Scholar 

  21. Sakaguchi S (2005) Naturally arising FoxP3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6:343–352

    Article  Google Scholar 

  22. Shevach EM (2004) Regulatory/suppressor T cells in health and disease. Arthritis Rheum 50:2721–2724

    Article  PubMed  CAS  Google Scholar 

  23. Kusakari C, Hozawa K, Koike S, Kyogoku M, Takasaka T (1992) MRL/Mp-lpr/lpr mouse as a model of immune-induced sensorineural hearing loss. Ann Otol Rhinol Laryngol Suppl 157:82–86

    PubMed  CAS  Google Scholar 

  24. Monk CR, Spachidou M, Rovis F, Leung E, Botto M, Lechler RI et al (2005) MRL/Mp CD4+,CD25-T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus. Arthritis Rheum 52:1180–1184

    Article  PubMed  CAS  Google Scholar 

  25. Yang M, Zheng J, Yang Q, Yao H, Chen Y, Tan H et al (2004) Frequency-specific association of antibodies against heat shock proteins 0 and 70 with noise-induced hearing loss in Chinese workers. Cell Stress Chaperones 9:207–213

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to An Ting Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xia, M., Zhang, H.B., Liu, F. et al. Impaired CD4+CD25+ regulatory T cell activity in the peripheral blood of patients with autoimmune sensorineural hearing loss. Eur Arch Otorhinolaryngol 265, 1027–1033 (2008). https://doi.org/10.1007/s00405-007-0565-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-007-0565-9

Keywords

Navigation