Functional Expression of a Costimulatory B7.2 (CD86) Protein on Human Salivary Gland Epithelial Cells that Interacts with the CD28 Receptor, but Has Reduced Binding to CTLA4

Abstract

B7 molecules expressed on classic APC play a critical role in the regulation of immune responses by providing activation or inhibitory signals to T cells, through the ligation with CD28 or CTLA4 receptors, respectively. We have recently described the expression of B7 molecules by the salivary gland epithelial cells (SGEC) of patients with Sjögren's syndrome (also termed autoimmune epithelitis). The role of such expression needs to be clarified. Thus, in the present study, we sought to address the existence and function of B7.2 proteins on cultured nonneoplastic SGEC lines derived from Sjögren's syndrome patients. The occurrence of B7.2 proteins on SGEC was verified by flow cytometry, immunocytochemistry, immunoprecipitation, and immunoblotting. The assessment of several cell lines in costimulation assays had revealed that the constitutive expression of B7.2 molecules is sufficient to provide costimulatory signals to anti-CD3-stimulated T cells. SGEC-derived costimulation induced IL-2-dependent proliferation of CD4(+) T cells, which was associated with low production of IL-2, but probably also with the secretion of yet undefined autocrine T cell growth factor(s). B7.2 proteins expressed by SGEC were found to display distinctive binding properties denoted by the functional interaction with CD28 receptor and reduced binding to CTLA4. Finally, the detection of a functional soluble form of B7.2 protein in cell-free culture supernatants of both SGEC and EBV-transformed B cell lines is demonstrated. These findings imply a critical role for epithelial cells in the regulation of local immune responses in the salivary glands.