Lymphocyte Subsets and HLA-DR Expression in Normal Pancreas and Chronic Pancreatitis

Differential and Mutually Exclusive Expression of CD95 and CD95 Ligand in Epithelia of Normal Pancreas and Chronic Pancreatitis

“…At the microtopographic level, CD95 induction in exocrine cells is paralleled by HLA-DR induction in these epithelia. Inflammationassociated HLA-DR induction in pancreatic epithelia has been previously described (Bedossa et al, 1990;Pavlovic et al, 1997). This setting strongly suggests an induction of these three molecules by inflammatory cytokines released by the local mononuclear infiltrate.…”

“…These infiltrates were shown to contain activated cytotoxic T cells (Hunger et al, 1997), suggesting a role of the immune system in the pathogenesis of acinar atrophy and local scarring. Induction of HLA-DR molecules was observed in parenchymal areas affected by chronic pancreatitis (Bedossa et al, 1990;Jalleh et al, 1993) and transcripts for MCP-1 chemokine have been detected in areas of early stage of chronic pancreatitis (Saurer et al, 2000). Local expression of T cell tropic chemokines may recruit T cells, the CD4 subset of which then may cognately interact with HLA-DR neoexpressing epithelial cells.…”

Loss of TGF-β signaling contributes to autoimmune pancreatitis

“…These cell types include B lymphocytes, activated T lymphocytes and macrophages, dendritic cells, glial cells, and thymic epithelial cells. Yet in certain autoimmune diseases, immune activity appears to be directed against cells that inappropriately express MHC class II molecules, such as β cells in the diabetic pancreas and thyroid cells in Grave's disease (28)(29)(30). TGF-β-null mice exhibit enhanced expression of MHC class II antigens at or before the onset of the inflammatory process, but the characteristic inflammatory lesions do not develop in TGF-β-null mice crossed into the severe combined immunodeficiency background (14).…”

Chronic pancreatitis, pseudotumors and other tumor-like lesions

“…32 The number of beta cells in these islets was found to be slightly reduced. 32 Immunohistological studies revealed that the duct epithelium commonly expresses HLA-DR and cytokines such as transforming growth factors alpha and beta (TGFa, TGFb1) and fibroblast growth factor (FGF) [33][34][35][36][37][38] TGFb1 and platelet derived growth factor (PDGF) were also found in fibroblasts, macrophages and/or platelets. 28,39,40 Myofibroblasts, which were recently named pancreatic stellate cells, are identified by their positivity for smooth muscle actin and desmin 15 ( Figure 8).…”

“…28,[41][42][43] The lymphocytic infiltrate consists largely of T lymphocytes. 33,34 The remaining acinar cells stain brightly for pancreatic enzymes and pancreatic stone protein. 44,45 The nerves that appear enlarged express particularly calcitonin-gene related peptide and substance P. 46 Both the endothelial cells and endocrine beta and alpha cells show strong endothelin-1 expression in chronic pancreatitis.…”