Background/aim: TGF-beta expression is increased in immune-mediated and fibrotic renal diseases and modulates the tubulointerstitial T-cell response. We examined whether TGF-beta changes the expression of PD-L1 and CD40 in the renal proximal tubular epithelial cell (TEC), and whether the activation of CD8(+) cytotoxic T cells (CTLs) is influenced by TGF-beta treatment of TECs.
Methods: Murine TECs were treated with TGF-beta or IFN-gamma. The expression of PD-L1 and CD40 was examined with RT-PCR and flow cytometry. To investigate if TGF-beta treatment influenced the antigen presentation capacity of TECs, OT-1 CTLs were co-incubated with TGF-beta-treated, OVA(257-264) peptide-pulsed congeneic TECs. The cytotoxicity of OT-1 CTLs was estimated by their capacity to produce IFN-gamma and their cytolytic activity.
Results: TGF-beta treatment lead to a transition in morphology of renal TECs and downregulated the basal and the IFN-gamma-stimulated PD-L1 expression in TECs. Interestingly, TGF-beta treatment of TECs increased the constitutive and IFN-gamma-induced CD40 expression. In contrast to IFN-gamma which reduced the CTL activity, TGF-beta treatment of TECs elevated the OVA-specific CTL response.
Conclusion: Our data show that TGF-beta changed the cellular phenotype and the expression of PD-L1 and CD40 on TECs and enhanced the activity of OVA peptide-specific CD8(+) T cells. TGF-beta may thereby play an important role in the progression of renal tubulointerstitial damage in CD8(+) T-cell-mediated renal diseases.
Copyright 2007 S. Karger AG, Basel.