Cellular and humoral immune responses in atrophic lymphocytic pancreatitisin German shepherd dogs and rough-coated collies

The most common cause for the clinical signs of exocrine pancreatic insuffi ciency (EPI) in dogs is pancreatic acinar atrophy (PAA). In the subclinical phase of EPI, before total atrophy occurs, exocrine pancreas is affected b y infiltrative lymphocytic inflammation, which gradually leads to selective destruction and atrophy of the acinar tissue. Here, we analyzed the role of cell-mediated and humoral immune mechanisms i n the pathogenesis of atrophic lymphocytic pancreatitis in German shepherd dogs and rough-coated collies. Pancreas biopsies and serum samples were obt ained from 12 dogs with subclinical EPI (SEPI), 13 dogs with clinical EPI a nd 13 healthy control dogs. Immunohistochemical analysis showed that, in the subclinical phase, the maj ority of the infiltrating lymphocytes were T-cells with an almost equal num ber of CD4+ 'T-helper' and CD8+ 'cytotoxic' T-lymphocytes, The distribution of the two lymphocyte subsets was different. Typically, the CD4+ cells wer e present in large cellular infiltrates in the affected parenchyma, and the scattered CD8+ cells had infiltrated both the affected and the normal pare nchyma. In sections where destruction of acinar parenchyma was present, the CD8+ T-cells were predominant. Ln cases of marked T-cell infiltration, CD7 9+ B-lymphocytes and plasma cells, and lysozyme-positive macrophages were a lso detected. Lymphoid follicle germinal centers with a majority of cells s taining positively for CD79 were found, The lymphocytic infiltration in the totally atrophic tissue of dogs with clinical EPI was less prominent. Indi rect immunofluorescence staining showed serum antibodies reacting weakly wi th pancreatic acinar cells in five out of nine dogs with subclinical and th ree out of 10 dogs with clinical EPI, but not in the control dogs. The results suggest that the tissue destruction is largely T-cell-mediated, although the presence of numerous B-lymphocytes and pancreas-specific anti bodies in the sera of some dogs indicate that humoral mechanisms are also i nvolved. In conclusion, this study suggests that the atrophic lymphocytic p ancreatitis in German shepherds and rough-coated collies is an autoimmune d isease. (C) 2000 Elsevier Science B.V. All rights reserved.