ANERGIC TH1 CLONES SPECIFIC FOR HEPATITIS-B VIRUS (HBV) CORE PEPTIDESARE INHIBITORY TO OTHER HBV CORE-SPECIFIC CD4(-CELLS IN-VITRO() T)

A strong and transient hepatitis B virus core (HBc)-specific CD4(+) T- cell response has been shown to be associated with viral elimination i n acute self-limited hepatitis B but to be absent in chronic hepatitis B, So far. little is known about immunological mechanisms involved in the regulation of the HBc-specific CD4(+) T cell response, We studied 28 patients with acute hepatitis B, and frequently a sudden decrease in the HBc-specific CD4(+) T-cell response was found between 4 and 8 w eeks after disease onset, Thirty-two CD4(+) T-cell clones specific for amino acids 50 to 69, 81 to 105, 117 to 131, or 141 to 165 of HBc wer e isolated from a patient shortly before the peripheral blood mononucl ear cell response to most HBc-derived peptides abruptly disappeared, T H1 clones, but not TH0 clones, could be anergized in vitro by stimulat ion with specific peptides even in the presence of costimulatory cells , Moreover, when anergic cells were mixed with responsive cells, the p roliferation of HBc-specific TH1 or TH0 clones was inhibited antigen s pecifically by anergic cells, The unusual susceptibility of HBc-specif ic TH1 clones to anergy induction in vitro as well as their potential to inhibit other HBc-specific TH1 and TH0 clones suggests that anergy induction may be involved in the downregulation of the virus-specific immune response during acute hepatitis B in vivo.