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Wiley, Clinical and Experimental Immunology, 3(179), p. 509-519

DOI: 10.1111/cei.12469



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Human renal tubular epithelial cells suppress alloreactive T-cell proliferation

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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IntroductionRenal tubular epithelial cells (TECs) are one of the main targets of alloreactive T-cells during acute rejection. We hypothesize that TECs modulate the outcome of allo-immunity by executing immunosuppressive effects in order to dampen the local inflammation. We studied whether TECs 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 PD-L1 and ICAM-1 with regard to TEC-related immunomodulatory effects.Materials and MethodsCD3/CD28 and allo-activated peripheral blood mononuclear cells were cocultured with activated TECs. We analysed CD4+ T-cell and CD8+ T-cell proliferation and apoptosis in the absence or presence of IDO inhibitor 1-L-MT, anti-PD-L1 and anti-ICAM-1. Further we examined whether inhibition of T-cell proliferation was cell-cell contact dependent.ResultsWe found that TECs dose-dependently inhibited CD4+ and CD8+ T-cell proliferation (P < 0.05). Activated TECs showed significantly increased IDO activity, and upregulated PD-L1 and ICAM-1 expression. Suppressed CD4+ and CD8+ T-cell proliferation was only partially restored or failed to restore using 1-L-MT. Activated TECs increased early and late apoptosis of proliferating CD4+ and CD8+ T-cells, only CD4+ 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 only affected CD4+ T-cell apoptosis and not the T-cell proliferation.DiscussionOur data show that TECs suppress both CD4+ and CD8+ 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-L1 in our system.