Impaired function of CD4+/CD25+ T regulatory lymphocytes characterizes the self-limited hepatitis A virus infection

J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 2):e105-10. doi: 10.1111/j.1440-1746.2007.05008.x. Epub 2007 Jul 20.

Abstract

Background and aim: Hepatitis A virus (HAV) causes a transient illness leaving permanent protection against reinfection. Few data are available on the regulatory mechanisms involved in the CD4+ T helper activation. We aimed to investigate the frequency and function of CD3+/CD4+/CD25+ T cells with regulatory function (Tregs) during acute HAV infection.

Methods: We enrolled 35 consecutive patients and 15 healthy donors, enumerated Tregs by flow cytometry assay and evaluated, after immunomagnetical sorting with magnetic beads, their ability to inhibit the proliferation of CD4+/CD25- T lymphocytes at different ratios (1:1, 1:10, 1:20).

Results: All patients had the usual course of infection. Our immunological analysis showed Tregs frequency in these patients (6.5% [range, 5-8.8%]; 36 [range, 10-87] cells) did not have any statistical difference compared with healthy donors (6% [range, 5-8%]; 48 (range, 23-71) cells), while their ability to suppress CD4+/CD25- was drastically reduced at different ratios (Mann-Whitney U-test; ratio 1:1, 93% vs 72%, z = -3.34, P < 0.0001; ratio 1:10, 86% vs 51%, z = -4.04, P < 0.001; ratio 1:20, 56% vs 30%, z = -3.43, P < 0.0001). After the seroconversion, CD4+/CD25+ frequency and function in HAV-infected patients did not differ from healthy individuals.

Conclusion: CD4+/CD25+ T cells seem to be impaired in their function during the HAV acute infection. This evidence might help to determine an optimal T helper cell immune network that is a predisposing factor for a self-limiting disease.

MeSH terms

  • Adult
  • CD3 Complex / analysis
  • CD4 Antigens / analysis*
  • Case-Control Studies
  • Cells, Cultured
  • Female
  • Hepatitis A / immunology*
  • Hepatitis A Virus, Human / immunology*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / analysis*
  • Lymphocyte Activation*
  • Male
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / virology

Substances

  • CD3 Complex
  • CD4 Antigens
  • Interleukin-2 Receptor alpha Subunit