Differential dynamics of the peripheral and intrahepatic cytotoxic T lymphocyte response to hepatitis B surface antigen
Differential dynamics of the peripheral and intrahepatic cytotoxic T lymphocyte response to hepatitis B surface antigen
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DOI：
10.1016/j.virol.2005.01.004
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发表时间：
2005-03-15
期刊：
影响因子：
3.7
通讯作者：
Chisari, FV
中科院分区：
文献类型：
--
作者：
Isogawa, M;Kakimi, K;Chisari, FV
本文研究了DNA免疫小鼠和表达B型肝炎病毒基因组的重组腺病毒（Ad-HBV）感染小鼠后，小鼠对B型肝炎表面抗原（HBsAg）的细胞毒性T淋巴细胞（CTL）应答的分布和动态。HBsAg特异性CTL在DNA免疫后优先在脾脏中积累，但在Ad-HBV感染后主要在肝内积累。在DNA致敏的小鼠中，对Ad-HBV的次级CTL应答的特征在于效应CTL从脾脏的快速消耗，以及它们在肝脏中的扩增，在肝脏中它们引起肝炎，分泌干扰素γ（IFN γ），并抑制HBV基因表达。HBsAg合成的抑制伴随着肝内产生IFN γ的CTL的消失和它们在脾脏中的重新积聚。这些数据表明，在慢性HBV感染的外周HBV特异性CTL的缺乏和功能缺陷的一个可能的解释，感染的严重程度可以恶化的预先存在的CTL反应，如果中和抗体也不存在。(C)2005年爱思唯尔公司All rights reserved.
The distribution and dynamics of the cytotoxic T lymphocyte (CTL) response to hepatitis B surface antigen (HBsAg) were studied in mice after intramuscular DNA immunization and after hepatic infection by a recombinant adenovirus that expresses the hepatitis B virus genome (Ad-HBV). CTLs specific for HBsAg accumulate preferentially in the spleen after DNA immunization but are primarily intrahepatic after Ad-HBV infection. The secondary CTL response to Ad-HBV in DNA-primed mice is characterized by rapid depletion of effector CTLs from the spleen, and their expansion in the liver where they cause hepatitis, secrete interferon gamma (IFNgamma), and inhibit HBV gene expression. Suppression of HBsAg synthesis is accompanied by disappearance of intrahepatic IFNgamma-producing CTLs and their reaccumulation in the spleen. The data Suggest a possible explanation for the paucity and functional deficiency of HBV-specific CTLs in the periphery during chronic HBV infection, and that the severity of infection can be worsened by a preexisting CTL response if neutralizing antibody is not also present. (C) 2005 Elsevier Inc. All rights reserved.