乙型肝炎病毒免疫耐受动物模型的建立与验证

ESTABLISHMENT AND VERIFICATION OF AN ANIMAL MODEL OF IMMUNOLOGICAL TOLERANCE AGAINST HEPATITIS B VIRUS

用鸭乙型肝炎病毒(DHBV)感染1d龄幼鸭建立了乙型肝炎免疫耐受动物模型,随访22周,鸭乙型肝炎病毒表面及前表面抗原(DHBs/presAg)及DHBV DNA阳性不变。在持续性感染鸭血清中未能检出抗DHBs/pres或抗鸭乙型肝炎核心(DHBc)抗体。用纯化的DHBs/pres Ag及DHBcAg与鸭外周血淋巴细胞作特异性淋巴细胞增殖试验,结果也未见阳性反应。以DHBs/presAg及DHBcAg分别免疫上述免疫耐受鸭,每3周1次。连续免疫5次,也未能刺激产生相应的抗体及特异性淋巴细胞增殖反应,从而首次建立并确证了1d龄鸭感染DHBV导致的免疫耐受动物模型。

In order to establish an animal model of immunologieal tolerance against Hepatitis B Virus (HBV), one-day old newly hatched ducklings were experimentally infected by injection of Duck Hepatitis B Virus (DHBV) positive serum simulating perinatal transmission of HBV. Both DHBs/presAg and DHBV DNA remained positive at 22 weeks follow-up. ELISA detected neither DHBs/prea antibody nor DHBc antibody in sera. Viral DHBs/presAg and DHBcAg antigen specific lymphocyte proliferation of DPBLs were also not observed. For further verification, purifed DHBs/presAg and DHBcAg were used to immunize the persistently infected ducks. Antibodies and lymphoproliferative responses to DHBs/presAg and DHBcAg were not detected. Thus, an animal model of immunologieal tolerance induced by DHBV infection in one-day old ducklings was well established and verified. These results may have implications for the study of immunologieal tolerance against HBV and future therapeutic strategies.