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

Abstract

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. 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. 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. 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.