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

B7 molecules expressed on classic APC play a critical role in the regulatio n of immune responses by providing activation or inhibitory signals to T ce lls, through the ligation with CD28 or CTLA4 receptors, respectively. We ha ve recently described the expression of B7 molecules by the salivary gland epithelial cells (SGEC) of patients with Sjogren's syndrome (also termed au toimmune epithelitis). The role of such expression needs to be clarified. T hus, in the present study, we sought to address the existence and function of B7.2 proteins on cultured nonneoplastic SGEC lines derived from Sjogren' s syndrome patients. The occurrence of B7.2 proteins on SGEC was verified b y flow cytometry, immunocytochemistry, immunoprecipitation, and immunoblott ing. The assessment of several cell lines in costimulation assays had revea led that the constitutive expression of B7.2 molecules is sufficient to pro vide costimulatory signals to anti-CD3-stimulated T cells. SGEC derived cos timulation induced IL-2-dependent proliferation of CD4(+) T cells, which wa s associated with low production of IL-2, but probably also with the secret ion of Set undefined autocrine T cell growth factor(s). B7.2 proteins expre ssed by SGEC were found to display distinctive binding properties denoted b y the functional interaction with CD28 receptor and reduced binding to CTLA 4. Finally, the detection of a functional soluble form of B7.2 protein in c ell-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.