Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice

Abstract

The nonobese diabetic mouse is a relevant model for insulin-dependent diabetes mellitus which results from the destruction of pancreatic beta cells by mononuclear cells infiltrating the islets of Langerhans. Other organs such as salivary glands display inflammatory infiltration. Using immunohistochemical and flow cytometry analyses, we have studied the expression of diverse homing and adhesion molecules in salivary glands and the pancreas in nonobese diabetic mice. In salivary glands, ICAM-1 was expressed by endothelial and dendritic cells within the lymphocytic infiltration. HEV-like structures expressing PNAd were observed in the areas of lymphocytic infiltration whereas MAdCAM-1 was absent. Lymphocytes infiltrating salivary glands expressed LFA-1 and Pgp-1 although Mel-14 Ag was absent. In infiltrated islets, ICAM-1 was expressed by endothelial cells, dendritic cells, and mononuclear cells. We confirm the presence of HEV-like structures expressing MAdCAM-1 and PNAd in inflamed islets. With regard to peripheral lymphocytes, the proportion of CD4 and CD8 cells expressing Mel-14 was decreased in the infiltrated islets, whereas the expression of LFA-1, Pgp-1, and LPAM-1/2 was increased. B lymphocytes exhibited up-regulation of LPAM-1/2. Moreover, the proportion of CD4, CD8, and B lymphocytes expressing CD69 was increased in the pancreas. These results indicate that first, infiltration of islets of Langerhans results at least partly from modifications of adhesion molecule expression in the pancreas, which allow extravasation of mononuclear cells into the islets via at least three different pathways; and second, that activated cells are concentrated in the infiltrates as compared with peripheral lymphoid organs.