TGF-beta treatment modulates PD-L1 and CD40 expression in proximal renal tubular epithelial cells and enhances CD8 cytotoxic T-cell responses

Nephron Exp Nephrol. 2007;107(1):e22-9. doi: 10.1159/000106506. Epub 2007 Jul 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / metabolism*
  • B7-H1 Antigen
  • CD40 Antigens / metabolism*
  • Cells, Cultured
  • Down-Regulation
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epitopes
  • Histocompatibility Antigens Class I / metabolism
  • Interferon-gamma / pharmacology
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / immunology
  • Kidney Tubules, Proximal / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Ovalbumin / immunology*
  • Peptides / metabolism*
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transforming Growth Factor beta / pharmacology*


  • B7-1 Antigen
  • B7-H1 Antigen
  • CD40 Antigens
  • Cd274 protein, mouse
  • Epitopes
  • Histocompatibility Antigens Class I
  • Membrane Glycoproteins
  • Peptides
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Ovalbumin