High spontaneous CD40 expression by salivary gland epithelial cells in Sjogren's syndrome: possible evidence for intrinsic activation of epithelial cells

CD40 is a surface protein originally identified on B cells. Its interaction with CD40L on T cells plays an important role in the activation, proliferation and differentiation of B cells. During the recent years, CD40 has been identified in an expanding list of hemopoietic and nonhemopoietic cells and has received an increased interest based on its role in a variety of cell-mediated responses and its potential to participate in the pathogenesis of chronic inflammatory disorders. Sjogren's Syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues.

To investigate the participation of CD40 in the pathogenesis of SS, the expression of this protein was studied in cultured non-neoplastic salivary gland (SG) epithelial cell (SGEC) lines as well as in minor SG biopsies obtained from 17 SS patients and 12 controls. Immunocytochemical and flow cytometric analysis has revealed the occurrence of constitutively expressed CD40 molecules on the surface of our long-term cultured SGEC lines, which could be further induced by IFNγ and IL-1β, but not TNFα, IL-4, IL-6, GM-CSF and IFNγ. In SGEC lines derived from SS patients, the spontaneous expression of membranous CD40 was significantly higher compared to controls (P < 0,001), which is likely suggestive of their activated status. In SG biopsies, CD40 was constitutively expressed by B cells, ductal epithelial cells and endothelial cells but not by other glandular cell types, such as acinar cells, myoepithelial cells and fibroblasts. In addition, CD40L staining was also detected in 30-50% of the infiltrating T cells in the biopsies of SS patients.

Our results possibly reveal the immunoregulatory potential of SGEC and lend further support to a model of intrinsic activation in salivary epithelia in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients.