Expression and regulation of human CD275 on endothelial cells in healthy and inflamed mucosal tissues

The CD275-CD278 costimulatory pathway is a new pathway for CD28-B7 family molecules involved in the effector phase of T-cell-mediated immune responses. Expression of CD275 in oral mucosa at healthy and disease states has not been examined. We generated monoclonal antibodies against human CD275 and investigated its expression and regulation in cultured tissue cell lines and oral mucosal tissues. CD275 on monocytes was efficiently upregulated by interleukin-4, while interferon-gamma abrogated this effect. CD275 on cultured endothelial cells (EC) was rapidly enhanced by tumour necrosis factor-alpha. In healthy oral mucosa, CD275 was not detected on keratinocytes, Langerhans cells or intraepithelial lymphocytes within the epithelium or on interstitial dendritic cells or lymphocytes in the sub-epithelium. Constitutive expression of CD275 on EC in the connective tissues was observed in healthy mucosa, but CD275 expression on EC in oral lichen planus was either upregulated or down regulated. Approximately 20% of the T cells found within infiltrating mononuclear cells in the sub-epithelium expressed high levels of the CD278 receptor. CD275 on lymphoid and nonlymphoid cells is positively or negatively regulated by various cytokines. Our results suggest that CD275 on EC is involved in the recruitment or extravasation of receptor-positive effector T cells into inflamed tissues.