Renal tubular epithelial cells modulate T-cell responses via ICOS-L and B7-H1

Kidney Int. 2005 Nov;68(5):2091-102. doi: 10.1111/j.1523-1755.2005.00665.x.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • B7-1 Antigen / genetics*
  • B7-H1 Antigen
  • Cell Communication / immunology
  • Cell Line, Transformed
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • Gene Expression / immunology
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Kidney Tubules / cytology*
  • Kidney Tubules / immunology*
  • Lymphocyte Activation / physiology
  • Membrane Glycoproteins / genetics*
  • Peptides / genetics*
  • Proteins / genetics*
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Membrane Glycoproteins
  • Peptides
  • Proteins
  • Interleukin-10
  • Interferon-gamma