BACKGROUND/AIMS: MHC molecules are upregulated on renal proximal tubular epithelial cells (TEC) under inflammatory conditions. This allows TEC to act as 'non-professional' antigen-presenting cells (APC). The aim of this study was to compare the costimulatory molecule expression pattern and the T cell activation capacity between renal TEC and professional APC, e.g. bone marrow-derived dendritic cells (BM-DC). METHODS: Flow cytometry analysis was used to study the costimulatory molecule surface expression on TEC or BM-DC. Ovalbumin-specific CD4 and CD8 T cell activation induced by TEC or BM-DC was compared, in terms of T cell proliferation, cytokine production and CTL activity. RESULTS: TEC did not constitutively express significant amounts of costimulatory molecules. Stimulation of TEC with IFN-beta or IFN-gamma, but not other tested cytokines, enhanced the expression of PD-L1, ICOS-L and CD40. Compared to BM-DC, TEC only induced suboptimal T cell activation. Blockade of PD-L1 on both APC strongly increased T cell activity. Furthermore, high PD-L1-expressing TEC were more resistant to the cytolysis by CTL. CONCLUSION: The low costimulatory molecule expression may explain the suboptimal T cell activation by TEC. The IFN-upregulated negative costimulatory molecule PD-L1 on TEC may play a protective role to limit tissue injury during renal parenchymal immune responses. (c) 2007 S. Karger AG, Basel.
BACKGROUND/AIMS: MHC molecules are upregulated on renal proximal tubular epithelial cells (TEC) under inflammatory conditions. This allows TEC to act as 'non-professional' antigen-presenting cells (APC). The aim of this study was to compare the costimulatory molecule expression pattern and the T cell activation capacity between renal TEC and professional APC, e.g. bone marrow-derived dendritic cells (BM-DC). METHODS: Flow cytometry analysis was used to study the costimulatory molecule surface expression on TEC or BM-DC. Ovalbumin-specific CD4 and CD8 T cell activation induced by TEC or BM-DC was compared, in terms of T cell proliferation, cytokine production and CTL activity. RESULTS:TEC did not constitutively express significant amounts of costimulatory molecules. Stimulation of TEC with IFN-beta or IFN-gamma, but not other tested cytokines, enhanced the expression of PD-L1, ICOS-L and CD40. Compared to BM-DC, TEC only induced suboptimal T cell activation. Blockade of PD-L1 on both APC strongly increased T cell activity. Furthermore, high PD-L1-expressing TEC were more resistant to the cytolysis by CTL. CONCLUSION: The low costimulatory molecule expression may explain the suboptimal T cell activation by TEC. The IFN-upregulated negative costimulatory moleculePD-L1 on TEC may play a protective role to limit tissue injury during renal parenchymal immune responses. (c) 2007 S. Karger AG, Basel.
Authors: M W H J Demmers; S S Korevaar; M Roemeling-van Rhijn; T P P van den Bosch; M J Hoogduijn; M G H Betjes; W Weimar; C C Baan; A T Rowshani Journal: Clin Exp Immunol Date: 2015-03 Impact factor: 4.330