Shirai M, Watanabe S, Nishioka M
Third Department of Internal Medicine, Kagawa Medical School, Japan.
Liver. 1990 Oct;10(5):302-12. doi: 10.1111/j.1600-0676.1990.tb00473.x.
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.
我们研究了纯化的重组乙型肝炎病毒（HBV）表面抗原（rHBsAg）和核心抗原（rHBcAg）对淋巴因子激活的杀伤细胞（LAK）活性的抑制作用。外周血单个核细胞（PBMC）或CD16 + CD3 - LAK前体细胞，在与白细胞介素-2（IL-2）和rHBsAg或rHBcAg预孵育72小时后，与仅存在IL-2或IL-2和大肠杆菌提取物时记录的结果相比，对Daudi细胞的LAK细胞毒性均显著降低。这种抑制作用呈剂量依赖性，并且在与这些HBV抗原进行24至72小时培养时呈时间依赖性。这种影响不是由贴壁细胞或其他辅助细胞介导的。与仅用IL-2或IL-2和大肠杆菌提取物培养72小时后的细胞反应水平相比，PBMC或LAK前体细胞在用IL-2和rHBsAg或rHBcAg培养72小时后的增殖反应显著减弱。在存在rHBsAg或rHBcAg的情况下，PBMC或LAK前体细胞中IL-2驱动的IL-2受体（p55）表达水平高于不存在这些HBV抗原时的水平。这些结果表明，HBsAg和HBcAg可能通过干扰LAK前体细胞对IL-2的增殖反应来抑制LAK活性的诱导，而不抑制细胞的IL-2受体表达。用重组IL-2培养的PBMC的细胞荧光分析显示，在存在这些HBV抗原的情况下，CD3 +和CD16 +细胞的百分比低于不存在抗原时的百分比。
