Integrins mediate adherence and migration of T lymphocytes on human peritoneal mesothelial cells

Abstract

We previously showed that a local immune response largely composed of type 1 T cells correlated with a favorable outcome of the peritonitis associated with peritoneal dialysis. To clarify how these subsets are recruited to the peritoneal cavity during inflammation, we measured integrin-mediated interactions between the T cells and human peritoneal mesothelial cells. Direct microscopy showed that lipopolysaccharide or peritoneal dialysis effluent stimulated the adherence of T cells to mesothelial cells, a process mediated by the integrins α6β1 and α4β1. Further, the migration of Th1 cell across human mesothelial cell monolayers grown on transwell surfaces was reduced by anti-α6β1 integrin antibody while that of Th2 cell was inhibited by an anti-α4 integrin antibody. Pretreatment with either lipopolysaccharide or rapid response peritoneal dialysis effluent stimulated T cell migration and this was significantly decreased by the α6β1 compared to the α4 antibody. These results suggest that integrins may play an important role in mediating selective T cell subset adhesion and migration across human peritoneal mesothelial cell monolayers and differential integrin expression and selective T cell subset recruitment during peritonitis may affect outcome. © 2008 International Society of Nephrology.