Sequential histopathology of pancreatic tissues in aly/aly mice.

C57BL/6J strain mice carrying the homozygous autosomal recessive mutation alymphoplasia (aly) lack peripheral lymph nodes and Peyer's patches and exhibit chronic infiltration of lymphocytes into various organs. Pancreatitis, one of the inflammatory lesions, is considered to be of autoimmune origin; however, the target autoantigens have not yet been determined. In this study, pancreatic tissues of male aly/aly mice and wild-type mice at 1-65 weeks of age were light- and electron-microscopically examined to investigate when and how pancreatitis develops. The results showed that macrophages had first appeared and remained in the lymphatic lumen at 3 weeks of age and then a lot of eosinophilic granulocytes infiltrated into the interlobular connective tissues at 5 weeks of age. After the subsidence of eosinophilic inflammation, macrophages and B220+ cells appeared at the perivascular tissues at 9 weeks of age. Thereafter, both CD4+ and CD8+ cells finally participated in the interstitial inflammation from 11 weeks of age. It was noted that these leukocytes had infiltrated into the perivascular interstitium rather than the parenchymal tissues during the course of pancreatitis, although a large parenchymal area was finally degenerated and replaced by adipose tissue.