Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells. Potential role in CD4+ T cell activation during Helicobacter pylori infection

Abstract

Human gastric mucosal epithelial cells display class II MHC, the expression of which is increased during Helicobacter pylori infection. These observations suggest that the gastric epithelium may participate as antigen- presenting cells (APC) during local immune responses. The increase in class [I MHC expression occurs in parallel with an elevation in gastric CD4+ T cell numbers within and adjacent to the epithelium. Since the expression of either B7-1 (CD80) or B7-2 (CD86) on APC is required for the activation of T cells, it was important to establish human gastric epithelial cells expressed those surface ligands. The expression of B7-1 and B7-2 was detected on human gastric epithelial cell lines and freshly isolated epithelial cells from gastric biopsies with specific antibodies. B7-2 expression was higher than B7-1 at both protein and transcript levels and was increased after crosslinking class II MHC molecules on IFNγ-treated epithelial cells and in cells pretreated with the combination of IFNγ and H. pylori. Similarly, B7- 2 expression was higher on gastric epithelial cells from H. pylori-infected tissues compared with those from uninfected specimens. To determine the function of these molecules on gastric epithelial cells, antibodies to B7.1 and B7-2 were shown to reduce the ability of the cells to stimulate alloreactive CD4+ T cells. These observations are the first to demonstrate that B7-1 and B7-2 are expressed on mucosal epithelial cells in situ. Thus, the expression of B7-1 and B7-2 by epithelial cells may allow them to act as APC in regulating local responses such as those that occur during infection with H. pylori.