Biliary atresia is associated with CD4+ Th1 cell-mediated portal tract inflammation

被引:157
作者
Mack, CL
Tucker, RM
Sokol, RJ
Karrer, FM
Kotzin, BL
Whitington, PF
Miller, SD
机构
[1] Childrens Hosp, Sect Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Pediat Liver Ctr, Denver, CO 80218 USA
[2] Childrens Hosp, Pediat Surg Sect, Dept Surg, Denver, CO 80218 USA
[3] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA
[4] Univ Colorado, Hlth Sci Ctr, Dept Med, Div Clin Immunol, Denver, CO 80262 USA
[5] Univ Colorado, Hlth Sci Ctr, Integrated Dept Immunol, Denver, CO 80262 USA
[6] Natl Jewish Med & Res Ctr, Denver, CO 80262 USA
[7] Northwestern Univ, Childrens Mem Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Chicago, IL 60614 USA
[8] Northwestern Univ, Feinberg Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA
[9] Northwestern Univ, Feinberg Sch Med, Interdept Immunobiol Ctr, Chicago, IL 60611 USA
关键词
D O I
10.1203/01.PDR.0000130480.51066.FB
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
A proposed mechanism in the pathogenesis of biliary atresia involves an initial virus-induced, progressive T cell-mediated inflammatory obliteration of bile ducts. The aim of this study was to characterize the inflammatory environment present within the liver of infants with biliary atresia to gain insight into the role of a primary immune-mediated process versus a nonspecific secondary response to biliary obstruction. Frozen liver tissue obtained from patients with biliary atresia, neonatal giant cell hepatitis, total parenteral nutrition (TPN)-related cholestasis, choledochal cysts, and normal control subjects was used for fluorescent immunohistochemistry studies of cellular infiltrates, cytokine mRNA expression, and in situ hybridization for localization of cytokine-producing cells. Immunohistochemistry revealed increases in CD8(+) and CD4(+) T cells and Kupffer cells (CD68(+)) in the portal tracts of biliary atresia. Reverse transcription-PCR analysis of biliary atresia tissue showed a Th1-type cytokine profile with expression of IL-2, interferon-gamma, tumor necrosis factor-a, and IL-12. This profile was not seen in normal, neonatal hepatitis or choledochal cyst livers but was present in TPN-related cholestasis. In situ hybridization revealed that the Th1 cytokine-producing cells were located in the portal tracts in biliary atresia and in the parenchyma of TPN-related cholestasis. A distinctive portal tract inflammatory environment is present in biliary atresia, involving CD4(+) Th1 cell-mediated immunity. The absence of similar inflammation in other pediatric cholestatic conditions suggests that the portal tract inflammation in biliary atresia is not a secondary response to cholestasis but rather indicates a specific immune response involved in the pathogenesis of biliary atresia.
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页码:79 / 87
页数:9
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