Kinetics of hepatitis B surface antigen-specific immune responses in acuteand chronic hepatitis B or after HBs vaccination: Stimulation of the in vitro antibody response by interferon gamma

Because cellular and humoral immune responses against the hepatitis B virus (HBV) surface antigen (HBs) might be crucial to overcome HBV infection, HB s-specific B- and T-cell responses of HBV patients and HBs vaccine recipien ts were analyzed quantitatively and functionally. In patients with acute he patitis B (AHB), transient high anti-HBs-secreting B-cell frequencies were observed early after clinical onset, whereas 1 patient who probably develop ed chronic infection and chronic HBV carriers had absent or weak B- and T-c ell responses. In HBs vaccine recipients, maximal HBs-specific B- and T-cel l responses were detected after the first injection that decreased graduall y before anti-HBs antibodies appeared in serum. Years after vaccination, an ti-HBs-secreting B cells were enriched in the bone marrow. After in vitro s timulation with HBsAg, peripheral blood mononuclear cells (PBMC) of only 1 of 5 acute and 1 of 6 chronic HBV patients, but of all 6 vaccine recipients , secreted varying amounts of interferon gamma (IFN-gamma), but no interleu kin-4 (IL-4) or IL-5. Furthermore, the addition of IFN-gamma, but not of IL -2, -4, -12, or IFN-alpha, resulted in strong increases of anti-HBs-secreti ng B cells in vaccine recipients and chronic carriers. In conclusion, circu lating anti-HBs-secreting B cells were significantly higher in early acute hepatitis B or early after HBs vaccination than in chronic hepatitis B and decreased in the follow-up as a result of compartmentalization to lymphoid tissues. Release of IFN-gamma by antigen-stimulated T cells might be critic al for anti-HBs formation.