Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13967
Starke, A; Wüthrich, R P; Waeckerle-Men, Y (2007). TGF-beta treatment modulates PD-L1 and CD40 expression in proximal renal tubular epithelial cells and enhances CD8 cytotoxic T-cell responses. Nephron. Experimental Nephrology, 107(1):e22-e29.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology|
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||22 Mar 2009 20:08|
|Last Modified:||23 Nov 2012 16:18|
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