期刊
LABORATORY INVESTIGATION
卷 81, 期 3, 页码 317-326出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.3780240
关键词
-
Acinar regression in chronic pancreatitis may be due to immune attack in parenchymal areas neoexpressing HLA-DR molecules. CD4(+)Th1 cytotoxic T cells induce apoptosis of their targets via oligomerizing CD95 (APO-1/Fas) death receptors on target cells by their CD95 ligand (CD95L). We determined the expression of GD95 and CD95L in epithelia of normal and chronically inflamed pancreatic tissues. We applied RT-PCR and Western blotting for CD95L expression profiles, serial frozen section immunohistochemistry to detect CD95, CD95L, and HLA-DR molecules, CD3, CD4, CD11c, and S-100 protein (S100p). Normal pancreases and chronic pancreatitis contain CD95L message and protein. Immunohistochemistry revealed a mutually exclusive expression of CD95 and CD95L. Physiologically, acini were CD95(-)/CD95L(+), ducts were CD95(-)/CD95L(-), and islets were CD95(-)/CD95L(+). In areas of lymphohistiocytic infiltration, mainly consisting of CD3(+)CD4(+) T cells and CD11c(+), CD4(+/-), /S100p(+) interstitial dendritic cells, and in areas of initial fibrosis, acini and ducts were HLA-DR+, acini CD95(-)/CD95L(-), and ducts CD95(+)/CD95L(-). Islet cells were CD95(-)/CD95L(+) in both conditions. IFN gamma levels in protein lysates, as measured by an immunoassay, were significantly higher in chronic pancreatitis than in normal pancreas (p < 0.0003). In vitro, IFN downmodulated CD95L message and protein in ASPC1 and BxPc3 pancreatic carcinoma cells. In conclusion, pancreatic epithelia differentially express CD95 and CD95L in a mutually exclusive manner. In chronic pancreatitis the CD95(-)/CD95L(+) status is conserved in islet cells even in the vicinity of lymphohistiocytic infiltrates, whereas it is lost in acini coexpressing HLA-DR. As a potential consequence, and possibly triggered by local release of IFN gamma, CD4(+)Th1 cells may cognately interact with and successfully attack exocrine cells by triggering CD95 on their target without being killed by epithelial, CD95L-mediated, counterattack.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据