title: Renal tubular epithelial cells modulate T-cell responses via ICOS-L and B7-H1.
abstract: BACKGROUND
  Renal tubular epithelial cells (TECs) play an active role in renal inflammation. Previous studies have demonstrated the capacity of TECs to modulate T-cell responses both positively and negatively. Recently, new costimulatory molecules [inducible T cell costimulator-L (ICOS-L) and B7-H1] have been described, which appear to be involved in peripheral T-cell activation.
  
  
  METHODS
  We characterized expression and regulation of costimulatory molecules on primary human TECs and the TEC line human kidney-2 (HK-2) with reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Immunohistochemistry was performed on human kidney biopsies. The capacity of TECs to modulate T-cell activation was studied in TEC/T-cell cultures.
  
  
  RESULTS
  We demonstrate that TECs express ICOS-L and B7-H1 in vitro and in vivo. Stimulation with interferon-gamma (IFN-gamma) resulted in increased expression of B7-H1, whereas ICOS-L expression was marginally increased upon stimulation with CD40L, with no effect of interleukin (IL-1), IL-17, or tumor necrosis factor-alpha (TNF-alpha). Furthermore, we show that TECs are able to costimulate T cells that have received signal-1 using alphaCD3 antibodies, inducing strong IL-10 production, which was partially mediated by ICOS-L. In contrast, B7-H1 appeared to be involved in inhibition of proliferation and cytokine synthesis. In addition, TECs were able to alter the cytokine profile of fully activated T cells, which were incubated with alphaCD3 and alphaCD28 antibodies, resulting in low IFN-gamma and high IL-10 production. This activity appeared to be independent of ICOS-L and B7-H1.
  
  
  CONCLUSIONS
  Interaction of tubular epithelial cells and kidney infiltrating T cells via ICOS-L and B7-H1 may change the balance of positive and negative signals to the T cells, leading to IL-10 production and limitation of local immune responses.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: de Haij
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Woltman
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Bakker
authors.forename: Sylvia W
authors.initials: SW
authors.lastname: Kamerling
authors.forename: Sandra W
authors.initials: SW
authors.lastname: van der Kooij
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D015703:Antigens, CD; D018122:B7-1 Antigen / Q000235:genetics*; D060890:B7-H1 Antigen; D002450:Cell Communication / Q000276:immunology; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D008562:Membrane Glycoproteins; D010455:Peptides; D011506:Proteins; D016753:Interleukin-10; D007371:Interferon-gamma