Akbar S M, Onji M, Inaba K, Yamamura K, Ohta Y
Third Dept. of Internal Medicine, Ehime University School of Medicine, Japan.
Immunology. 1993 Mar;78(3):468-75.
The experiments presented here were performed to evaluate immune responsiveness of hepatitis B virus (HBV)-transgenic mice (transgenic mice), as a model of HBV-carrier state to a T-cell-dependent antigen, keyhole limpet haemocyanin (KLH). The transgenic mice which were completely unresponsive to hepatitis B surface antigen (HBsAg), responded poorly to KLH. The levels of anti-KLH antibodies (Ab) produced in vivo were significantly lower in transgenic mice compared with the normal control mice at respective immunizing doses of KLH. In addition, a little or no anti-KLH Ab production was detected in culture supernatants of KLH-primed transgenic mice spleen cells. KLH-primed T cells from normal and transgenic mice induced anti-KLH Ab production from transgenic B cells in the presence of antigen-presenting spleen adherent cells (SAC) from normal mice, but not those from transgenic mice. Depletion of dendritic cells from normal mice-derived SAC completely abrogated the anti-KLH Ab response in transgenic spleen cell culture and their addition to the culture restored the response. Low efficiency of transgenic dendritic cells was demonstrated in sodium periodate (NaIO4)-induced non-specific and allogenic antigen-induced T-cell proliferation. Finally, cytofluorometric analyses showed a reduced Ia antigen expression on transgenic dendritic cells. These results indicate that low responsiveness of transgenic mice in specific-antibody response is not due to functional defects in T cells or B cells but rather to a defect of antigen-presenting activity of dendritic cells.
此处呈现的实验旨在评估作为乙肝病毒（HBV）携带者状态模型的HBV转基因小鼠对T细胞依赖性抗原——钥孔戚血蓝蛋白（KLH）的免疫反应性。对乙肝表面抗原（HBsAg）完全无反应的转基因小鼠，对KLH的反应也很差。在各自的KLH免疫剂量下，转基因小鼠体内产生的抗KLH抗体（Ab）水平与正常对照小鼠相比显著降低。此外，在经KLH致敏的转基因小鼠脾细胞的培养上清液中，检测到很少或没有抗KLH Ab产生。在存在来自正常小鼠而非转基因小鼠的抗原呈递脾黏附细胞（SAC）的情况下，来自正常和转基因小鼠的经KLH致敏的T细胞诱导转基因B细胞产生抗KLH Ab。从正常小鼠来源的SAC中去除树突状细胞完全消除了转基因脾细胞培养中的抗KLH Ab反应，而将它们添加到培养物中可恢复反应。在高碘酸钠（NaIO4）诱导的非特异性和同种异体抗原诱导的T细胞增殖中，证明了转基因树突状细胞的效率低下。最后，细胞荧光分析显示转基因树突状细胞上Ia抗原表达降低。这些结果表明，转基因小鼠在特异性抗体反应中的低反应性不是由于T细胞或B细胞的功能缺陷，而是由于树突状细胞的抗原呈递活性缺陷。
