Renal allograft rejection: induction and function of adhesion molecules on cultured epithelial cells

SUMMARY The interaction of graft‐infiltrating immune cells with donor parcnchymal cells is an important early event in allograft rejection. This binding is stabilized by interaction of antigen‐independent ‘adhesion’ molecules expressed on the two cell types. As lhe level ofexpressionofthese molecules can be altered during inflammation, a series of experiments was prcrformed to examine the effects of the inflammiiiory cytokines intcrfcron‐gamma (IFN‐;); ind tumour necrosis factor‐alpha (TNF‐a) on adhesion molecules expressed by cultured human renal tubular epithelial cells. These cells constitutively expressed ICAM‐l and LFA‐. Incubation with IFN‐y increased expression of ICAM‐i but had no significant effect on expression of LFA‐3 (<005). Incuhation with TNF‐a increased expression of both ICAM‐1 and LFA‐3; IFN‐ysynergizcd withTNF‐ot to further augment expression of these molecules. Peripheral blood lymphocyles (PBL) showed an enhanced binding to allogeneic renal epithelial cell monolayers which had been pretreated with IFN‐yorTNF‐x. MoAbs specific for ICAM‐l or its ligand LFA‐1 inhibited adhesion of PBL lo either IFN‐;‐ or TNF‐apretreated renal cells. By contrast, antibodies specific for LFA‐3 or its ligand CD2 only significantly blocked PBL adhesion to renal cells which had been pretrealed with TNF‐x. Combination of antibodies spccitic lor multiple components of the adhesion systems produced greater inhibition of adhesion than was produced by any single MoAb. These results suggest thai the inliammatory cytokines IFN‐7 and TNF‐a up‐regulatc expression of functional lCAM‐1 and LFA‐3 molecules which can augment ihe binding of potentially graft‐damaging lymphoid cells to renal tubular epithelial eells.