Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T cells from low- and high-antibody responders in vaccinated humans.

It is well known that individuals with low, or lack of, antibody production in response to hepatitis B surface antigen (HBsAg) exist in the human population. We have previously reported that HLA class I and class II genes are both involved in antibody production to HBsAg, and that specific alleles of HLA are associated with low and high antibody production. To elucidate further the mechanisms by which the diversity of antibody production to HBsAg is generated in humans, a total of 146 T-cell clones specific for HBsAg were produced from six healthy vaccinees (three low- and three high-antibody responders) and were examined for cytokine production and HLA restriction. It was found that the majority of the T-cell clones from the low-antibody responders were Th1- or Th0-like T cells (62% or 19%, respectively), whereas the majority of T-cell clones from the high-antibody responders were Th2-like T cells (77%), suggesting predominant expansion of Th1/Th0- and Th2-like T cells specific for HBsAg in the low- and high-antibody responders, respectively. This is the first evidence that the diversity of the response to HBsAg in humans is controlled by the activation of functionally distinct CD4+ T-cell subsets, i.e., Th0, Th1, or Th2 T cells.