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


CONCLUSIONS
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.
Waeckerle-Men
Ying
Y
Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich-Irchel, Zürich, Switzerland. ying.waeckerle-men@access.uzh.ch
Starke
Astrid
A
Wahl
Patricia R
PR
Wüthrich
Rudolf P
RP
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D060945:Inducible T-Cell Co-Stimulator Ligand; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D019013:CD40 Antigens; C498919:Cd274 protein, mouse; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D008562:Membrane Glycoproteins; D010455:Peptides; D011506:Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D010047:Ovalbumin