Limited costimulatory molecule expression on renal tubular epithelial cells impairs T cell activation

Kidney Blood Press Res. 2007;30(6):421-9. doi: 10.1159/000110578. Epub 2007 Oct 26.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / metabolism*
  • B7-H1 Antigen
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • CD40 Antigens / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Inducible T-Cell Co-Stimulator Ligand
  • Interferon-beta / pharmacology
  • Interferon-gamma / pharmacology
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism*
  • Lymphocyte Activation / physiology*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / metabolism
  • Peptides / metabolism*
  • Proteins / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*

Substances

  • B7-1 Antigen
  • B7-H1 Antigen
  • CD40 Antigens
  • Cd274 protein, mouse
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Icosl protein, mouse
  • Inducible T-Cell Co-Stimulator Ligand
  • Membrane Glycoproteins
  • Peptides
  • Proteins
  • Interferon-beta
  • Interferon-gamma
  • Ovalbumin