Inhibitory effects of hepatitis B virus antigen on induction of lymphokine-activated killer cell activity.

We investigated the inhibitory effects of purified recombinant hepatitis B virus (HBV) surface antigen (rHBsAg) and core antigen (rHBcAg) on lymphokine-activated killer cell (LAK) activity. Either peripheral blood mononuclear cells (PBMCs) or CD16+ CD3- LAK precursors, both of which were pre-incubated with interleukin-2 (IL-2) and rHBsAg or rHBcAg for 72 h, showed a significant decrease in LAK cytotoxicity against Daudi cells, in comparison to the results recorded in the presence of IL-2 alone, or IL-2 and E. coli extracts. This inhibitory effect was dose-dependent and was observed to be time-dependent from 24 to 72-h-cultures with these HBV antigens. This influence was not mediated with either adherent cells or other accessory cells. The proliferative reaction of either PBMCs or the LAK precursors after being cultured with IL-2 and rHBsAg or rHBcAg for 72 h was significantly diminished compared with the levels of reaction of those cells after a 72-h culture with IL-2 alone or with IL-2 and E. coli extracts. The levels of IL-2-driven IL-2 receptor (p55) expression of either PBMCs or the LAK precursors in the presence of rHBsAg or rHBcAg were higher than the levels seen in the absence of these HBV antigens. These results suggest that HBsAg and HBcAg may inhibit the induction of LAK activity by interfering with the proliferative reaction of the LAK precursors to IL-2 without inhibiting the IL-2 receptor expression of the cells. Cytofluorographic analysis of PBMCs, cultured with rIL-2, showed lower percentages of CD3+ and CD16+ cells in the presence of these HBV antigens than those in the absence of antigens.