Polarized expression and function of the costimulatory molecule CD58 on human intestinal epithelial cells

Background & Aims: Intestinal epithelial cells (IECs) can process foreign protein antigens and display antigenic peptides to CD4(+) T lymphocytes via HLA class II molecules. The purpose of this study was to determine the nature of the second, or costimulatory, signal provided by IECs, Methods: We investigated surface expression of the costimulatory molecules CD58 (LFA-3), CD80 (B7-1), and CD86 (B7-2) by using flow cytometry, confocal microscopy, and vectorial biotinylation, Antibodies specific for CD58, CD80, and CD86 were used in blocking experiments to assess the role of these molecules in providing a costimulatory signal to CD4(+) T cells by IECs, Results: CD58, but not CD80 or CD86, was observed to be expressed constitutively on both native IECs and in the IEC lines T84 and HT-29, The surface expression of CD58 was highly polarized and restricted to the basolateral surface of the cell. Antibodies against CD58, but not CD80 or CD86, inhibited the stimulation of CD4(+) T-cell proliferation mediated by IECs, Conclusions: CD58 is expressed by polarized IECs in a topologically restricted manner at the region of T-cell contact and can function as a costimulatory molecule in HLA class II-mediated antigen presentation.