Z Gastroenterol 2011; 49 - P4_03
DOI: 10.1055/s-0030-1269658

HBsAg-specific regulatory T cells are present in patients with chronic HBV infection

T Bauer 1, JJ Wenzel 1, B Huber 1, W Jilg 1
  • 1Institut für Medizinische Mikrobiologie und Hygiene, Regensburg

We analysed the frequency and phenotypic characteristics of HBsAg-specific regulatory T cells (HBsAg-Treg) in individuals with different HBV infection status and investigated their effect on cellular immune responses as well as the mechanisms underlying their regulatory function. In addition we assessed, whether HBsAg-Treg have an inhibitory effect on anti-HBs production by suppressing corresponding T helper cell functions. A total of 45 subjects including patients with chronic (n=16) and resolved (n=10) hepatitis B, solely anti-HBc-positive (n=9) and vaccinated (n=10) individuals were tested. Immune responses were determined by Elispot analysis of HBsAg-specific T cells and anti-HBs-producing B cells. HBsAg-Treg were detectable in 9/16 chronic carriers and 4/9 solely anti-HBc-positive individuals, but neither in patients with resolved HBV infection nor in vaccinated individuals. Circulating HBsAg-Treg show a CD4+/CD25+ phenotype, produce exclusively IL-10 and suppress function of HBsAg-specific CD4+ effector T cells in vitro. Suppression of effector cells determined in depletion and IL-10 neutralization experiments is dose-dependent, requires direct cell-cell contact, and is independent of IL-10. T cell epitope mapping revealed the same epitope specificity for HBsAg-Treg and CD4+ effector T cells, respectively. Depletion of CD25+/CD4+ Treg enhances HBsAg-specific effector T cell responses, however it has no impact on the number of detectable anti-HBs-secreting B cells in all tested groups. Our data suggest that HBsAg-specific Treg are exclusively induced in patients with chronic HBV infection. They may be responsible for or at least contribute to the inadequate cellular immune response against HBsAg by dampening effector T cell responses. The inability of chronic carriers to develop anti-HBs, however, does not seem to be determined by the presence of HBsAg-Treg only.

HBV - Hepatitis B - chronic HBV infection - regulatory T cells