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- Title
Renal tubular PD-L1 (CD274) suppresses alloreactive human T-cell responses.
- Authors
Starke, Astrid; Lindenmeyer, Maja T.; Segerer, Stephan; Neusser, Matthias A.; Rüsi, Barbara; Schmid, Daniel M.; Cohen, Clemens D.; Wüthrich, Rudolf P.; Fehr, Thomas; Waeckerle-Men, Ying
- Abstract
Renal proximal tubular epithelial cells, a target of infiltrating T cells during renal allograft rejection, may be protected from this injury by the cell surface protein CD274 (also termed PD-L1 for programmed death ligand 1). The co-inhibitory molecules PD-L1 (CD274) and PD-L2 (CD273) are ligands of PD-1 (programmed death 1; CD279). Here we determine the functional role of PD-1/PD-L pathways in human renal allograft rejection. Treatment of human primary tubular epithelial cells with interferon-β and -γ caused a dose-dependent and synergistic increase of PD-L1 and PD-L2 expression. Blockade of surface PD-L1, but not PD-L2, on interferon-treated tubular epithelial cells resulted in a significant increase in CD4+ T-cell proliferation and cytokine production by CD4+ and CD8+ T cells. The expression of PD-L1, PD-L2, and PD-1 mRNA and protein was upregulated in biopsies of patients with renal allograft rejection compared to the respective levels found in the pre-transplant biopsies. Induction of PD-L1 was significantly associated with acute vascular rejection. Our study suggests that the renal epithelial PD-1/PD-L1 pathway exerts an inhibitory effect of on alloreactive T-cell responses. The upregulation of PD-L1 on proximal tubular epithelial cells in patients with acute allograft rejection may reduce T-cell-mediated injury.
- Subjects
EPITHELIAL cells; GRAFT rejection; T cells; HOMOGRAFTS; INTERFERONS; TRANSPLANTATION immunology
- Publication
Kidney International, 2010, Vol 78, Issue 1, p38
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2010.97