Differential and mutually exclusive expression of CD95 and CD95 ligand in epithelia of normal pancreas and chronic pancreatitis

Acinar regression in chronic pancreatitis may be due to immune attack in pa renchymal 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 inflame d pancreatic tissues. We applied RT-PCR and Western blotting for CD95L expr ession profiles, serial frozen section immunohistochemistry to detect CD95, CD95L, and HLA-DR molecules, CD3, CD4, CD11c, and S-100 protein (S100p). N ormal 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(-)/CD 95L(-), and islets were CD95(-)/CD95L(+). In areas of lymphohistiocytic inf iltration, 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(+)/CD 95L(-). Islet cells were CD95(-)/CD95L(+) in both conditions. IFN gamma lev els in protein lysates, as measured by an immunoassay, were significantly h igher in chronic pancreatitis than in normal pancreas (p < 0.0003). In vitr o, IFN<gamma> downmodulated CD95L message and protein in ASPC1 and BxPc3 pa ncreatic carcinoma cells. In conclusion, pancreatic epithelia differentiall y express CD95 and CD95L in a mutually exclusive manner. In chronic pancrea titis the CD95(-)/CD95L(+) status is conserved in islet cells even in the v icinity of lymphohistiocytic infiltrates, whereas it is lost in acini coexp ressing HLA-DR. As a potential consequence, and possibly triggered by local release of IFN gamma, CD4(+)Th1 cells may cognately interact with and succ essfully attack exocrine cells by triggering CD95 on their target without b eing killed by epithelial, CD95L-mediated, counterattack.