Cellular immune responses after successful hepatitis B immunization in patients transplanted for HBV-related diseases: Existence of HBsAg-specific regulatory T cells

Patients after liver transplantation for hepatitis B related diseases are currently treated lifelong with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine failed.

A study with a new adjuvanted hepatitis B vaccine (HBsAg-AS02) was exceptionally successful leading to a hightitered longlasting antibody response in 80% of all vaccinees (Bienzle et al., Hepatology. 2003 Oct;38(4): 811–9). In a continuative study we analysed cellular immune responses of the successfully vaccinated participants (n=16) 6 to 12 months after completion of the study. Furthermore, as the AS02-vaccine has not yet been licensed, we tested, whether a hepatitis B vaccine is capable to booster existing immune responses.

HBsAg-specific CD4+ T lymphocytes could be detected in 14 of 16 AS02-vaccinees tested. Unexpectedly these T cells produce almost exclusively IL–10 and have a CD4+/CD25+ phenotype thus representing regulatory T cells (TReg). Eleven of the 16 patients received a booster vaccination 19–31 months after the last AS02 vaccination. Nine showed a switch to a Th1-type immune response two weeks after revaccination with HBsAg-specific T cells secreting IL–2, IFN-γ and TNF-α. Four weeks after revaccination four patients continued to show a Th1-type immune response whereas in five patients TReg were again detectable.

In conclusion our study prove the existence of HBsAg-specific TReg within the group of hepatitis B vaccinated liver transplant recipients. Vaccine-induced immune responses are boosterable and revaccination is accompanied by the disappearance of the TReg population and the temporary appearance of HBsAg-specific T cells with a Th1-type cytokine profile.