IS A FUNCTION OF THE SECRETED HEPATITIS-BE ANTIGEN TO INDUCE IMMUNOLOGICAL-TOLERANCE INUTERO
IS A FUNCTION OF THE SECRETED HEPATITIS-BE ANTIGEN TO INDUCE IMMUNOLOGICAL-TOLERANCE INUTERO
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DOI：
10.1073/pnas.87.17.6599
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
MCLACHLAN, A
中科院分区：
文献类型：
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作者：
MILICH, DR;JONES, JE;MCLACHLAN, A
乙肝病毒携带者母亲所生的婴儿，如果表达一种名为HBeAg的核衣壳抗原的分泌型，总是会持续感染。为了研究免疫耐受机制在新生儿慢性感染中的作用，我们产生了表达HBeAg的转基因小鼠。表达HBeAg的转基因小鼠在T细胞水平上对HBeAg和非分泌型核衣壳蛋白(乙肝核心抗原/HBcAg)均有耐受性。转基因小鼠在体内和体外不产生抗HBeAg抗体，但不产生抗HBc抗体。体内对HBc/HBe T细胞决定簇的耐受性和抗HBc抗体的产生与携带者母亲所生新生儿的免疫状态平行。研究还表明，T细胞对HBcAg/HBeAg的耐受性的维持需要耐受原的持续存在，并且在没有耐受原的情况下持续存在16周。T细胞对HBcAg/HBeAg耐受性的可逆性可能解释了感染年龄和病毒耐药率之间的负相关。这些观察结果表明，HBeAg的一个功能可能是在子宫内诱导免疫耐受。HBeAg的表达可能代表了一种病毒策略，以确保围产期感染后的持久性。
Infants born to hepatitis B virus carrier mothers, who express a secreted form of the nucleocapsid antigen designated HBeAg, invariabily become persistently infected. To investigate the role of immunologic tolerance mechanisms in chronic infection of the newborn, we have generated HBeAg-expressing transgenic mice. HBeAg-expressing transgenic mice were tolerant to both HBeAg and the nonsecreted nucleocapsid (hepatitis B cor antigen/HBcAg) at the T-cell level. Transgenic mice did not produce antibody to HBeAg but did not produce anti-HBc antibody in vivo and in vitro. The coexistence of tolerance to HBc/HBe T-cell determinants and anti-HBc antibody production in vivo parallels the immunologic status of neonates born to carrier mothers. It was also demonstrated that the maintenance of T-cell tolerance to HBcAg/HBeAg required the continued presence of the tolerogen and in its absence persisted for < 16 weeks. The reversibility of T-cell tolerance to HBcAg/HBeAg may explain the inverse correlation between age of infection and rates of viral persistance. These observations suggest that a function of the HBeAg may be to induce immunologic tolerance in utero. Expression of HBeAg may represent a viral strategy to guarantee persistence after perinatal infection.