Study on the immune tolerance status and blood biochemical index of hepatitis B virus transgenic mice / 中华传染病杂志

ABSTRACT

ObjectiveTo research the hepatitis B virus (HBV) replication and immune tolerance status of transgenic mice for elucidating the pathogenesis of hepatitis B and evaluating new drugs against HBV.Methods SPE grade HBsAg negative nontransgenic and transgenic mice with the same genetic background were recruited in this study.HBsAg,HBeAg and HBV DNA were detected by chemiluminescent method.Pre-S1 and HBcAg were detected by enzyme linked immunosorbont assay (ELISA).Liver pathology was examined and HBsAg expressions at different stages were determined by immunohistochemical staining.The lymphocyte proliferation of mice was detected by flow cytometry and interferon (IFN)γ-producing T lymphocytes was determined by enzyme linked immunospot (ELISPOT).The expressions of Toll-like receptor (TLR)2 and TLR9 in splenocyte suspension and splenic dendrite cells (DC) were determined by double-labeling immunofluorescence.The data were analyzed by t test and F test.ResultsHBsAg,preS1,HBeAg,HBcAg were expressed and HBV DNA was replicated in HBV transgenic mice,while anti-HBs,anti-HBc,and anti-HBe were all negative.There were no obvious pathological changes in liver tissues.HBsAg was expressed in cytoplasm and HBcAg in nucleus of hepatocytes.After stimulated with HBsAg,T lymphocyte proliferation capacity of HBV transgenic mice was (697.6±67.3) cpm,which was much lower than that of nontransgenic mice [( 1315.5 ±191.6) cpm].The number of spot forming cells of IFNγ-producing splenocytes from transgenic mice after HBsAg stimulation was 8.25 ± 1.10,which was obviously lower than that of nontransgenic mice (28.50±4.21) (F=155.967,P=0.000).The expressions of CD11c+,TLR2 and TLR9 on DC from both HBV transgenic and nontransgenic mice were not different significantly (all P＞0.05).The HBsAg expressions in liver tissues were observed in 18-day-old fetal mice and 1-day-old newborn mice.ConclusionsThe HBV transgenic mice can express HBV-related antigens,and are immune tolerant to the antigens.The innate and acquired immunity of the HBV transgenic mice are normal,which is similar to chronic asymptomatic HBV carriers of human.Therefore,HBV transgenic mouse is an ideal animal model.