Human renal tubular epithelial cells suppress alloreactive T cell proliferation

Summary Renal tubular epithelial cells ( TEC s) are one of the main targets of alloreactive T cells during acute rejection. We hypothesize that TEC s modulate the outcome of alloimmunity by executing immunosuppressive effects in order to dampen the local inflammation. We studied whether TEC s possess immunosuppressive capacities and if indoleamine 2,3‐dioxygenase ( IDO ) might play a role in suppressing T cell alloreactivity. Next, we studied the role of programmed death ligand 1 ( PD ‐ L 1) and intercellular adhesion molecule‐1 ( ICAM ‐1 with regard to TEC ‐related immunomodulatory effects. CD 3/ CD 28 and alloactivated peripheral blood mononuclear cells were co‐cultured with activated TEC s. We analysed CD 4 + and CD 8 + T cell proliferation and apoptosis in the absence or presence of IDO inhibitor 1‐methyl‐ L ‐tryptophan (1‐ L ‐ MT ), anti‐ PD ‐ L 1 and anti‐ ICAM ‐1. Further, we examined whether inhibition of T cell proliferation was cell–cell contact‐dependent. We found that TEC s dose‐dependently inhibited CD 4 + and CD 8 + T cell proliferation ( P  < 0·05). Activated TEC s showed significantly increased IDO activity and up‐regulated PD ‐ L 1 and ICAM ‐1 expression. Suppressed CD 4 + and CD 8 + T cell proliferation was only partially restored or failed to restore using 1‐ L ‐ MT . Activated TEC s increased early and late apoptosis of proliferating CD 4 + and CD 8 + T cells; only CD 4 + T cell apoptosis was statistically affected by 1‐ L ‐ MT . Transwell experiments revealed that TEC ‐mediated immunosuppression is cell–cell contact‐dependent. We found that anti‐ ICAM ‐1 affected only CD 4 + T cell apoptosis and not T cell proliferation. Our data show that TEC s suppress both CD 4 + and CD 8 + T cell proliferation contact dependently. Interestingly, inhibition of proliferation and enhancement of apoptosis of T cell subsets is differentially regulated by indoleamine 2,3‐dioxygenase and ICAM ‐1, with no evidence for the involvement of PD ‐ L 1 in our system.