Role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection.
Role of type 1 versus type 2 immune responses in liver during the onset of chronic woodchuck hepatitis virus infection.
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慢性土拨鼠肝炎病毒感染发作期间肝脏中 1 型与 2 型免疫反应的作用。
DOI：
10.1053/jhep.2003.50154
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Cote,PaulJ
中科院分区：
文献类型：
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作者：
Wang,Yun;Menne,Stephan;Jacob,JamesR;Tennant,BudC;Gerin,JohnL;Cote,PaulJ
比较了自限性（解决）和慢性新生儿土旱鼠肝炎病毒（WHV）感染期间肝脏的免疫反应信使rna （mRNA）。在感染后第14周（急性中期），肝脏中白细胞标志物（CD3、CD4、CD8）、1型细胞因子和相关转录因子（IFN‐γ、TNF‐α、STAT4、T‐bet）和IL‐10的mrna均因感染消退而升高，但其他1型（IL‐2）和2型（IL‐4、STAT6和GATA3）标志物的mrna仍保持在基线水平。在大多数情况下，IFN - γ和TNF - α mrna的共表达增加与肝内WHV共价闭合环状DNA （cccDNA）水平降低相关。在感染后的同一时间点，最终进展为慢性感染的土旱獭肝脏中CD和1型mrna的基线水平或略有升高，与未感染土旱獭相比，这些水平明显较低（或升高频率较低）。早些时候，在第8周，两种结果设置之间没有差异。在这些早期时间点和慢性感染的后期阶段（15个月），携带者肝脏中的2型mrna保持在基线水平，即使升高，也不会超过解决土旱獭的水平。总之，新生儿慢性WHV感染的发生和维持与肝脏中1型应答的拮抗2型免疫调节无关。因此，慢性发展与肝内CD反应的原发性缺乏有关，特别是涉及CD8+T淋巴细胞，以及细胞外（细胞因子）和细胞内（转录）1型反应介质。这对人类慢性乙型肝炎病毒（HBV）感染的未来治疗具有相关意义。(肝脏病学2003;37:771 780。)
Immune response messenger RNAs (mRNA) were compared in liver during self‐limited (resolved) and chronic neonatal woodchuck hepatitis virus (WHV) infection. At week 14 postinfection (mid‐acute phase), mRNAs for leukocyte markers (CD3, CD4, CD8), type 1 cytokines and related transcription factors (IFN‐γ, TNF‐α, STAT4, T‐bet), and IL‐10 were increased in livers from resolving infections, but mRNAs of other type 1 (IL‐2) and type 2 (IL‐4, STAT6, and GATA3 markers remained at baseline levels. Increased coexpression of IFN‐γ and TNF‐α mRNAs correlated in most cases with lower levels of intrahepatic WHV covalently closed circular DNA (cccDNA). At the same time point postinfection, livers from woodchucks that eventually progressed to chronic infection had baseline or slightly elevated levels of CD and type 1 mRNAs, which were significantly lower (or elevated less frequently) compared with resolving woodchucks. Earlier, at week 8, there were no differences between the two outcome settings. During these early time points and at a later stage in chronic infection (15 months), type 2 mRNAs in carrier liver remained at baseline levels or, when elevated, were never in excess of those in resolving woodchucks. In conclusion, the onset and maintenance of neonatal chronic WHV infection are not associated with antagonistic type 2 immunoregulation of type 1 responses in liver. Accordingly, chronicity develops in association with a primary deficiency in the intrahepatic CD responses, especially involving CD8+T lymphocytes, and in both extracellular (cytokine) and intracellular (transcriptional) type 1 response mediators. This has relevant implications for future treatment of chronic hepatitis B virus (HBV) infection in humans. (Hepatology 2003;37:771‐780.)