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

Simone De Haij, Andrea M. Woltman, Leendert A. Trouw, Astrid C. Bakker, Sylvia W. Kamerling, Sandra W. Van Der Kooij, Lieping Chen, Richard A. Kroczek, Mohamed R. Daha, Cees Van Kooten

Research output: Contribution to journalArticlepeer-review

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-γ (IFN-γ) 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-α (TNF-α). Furthermore, we show that TECs are able to costimulate T cells that have received signal-1 using αCD3 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 αCD3 and αCD28 antibodies, resulting in low IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)2091-2102
Number of pages12
JournalKidney International
Volume68
Issue number5
DOIs
StatePublished - Nov 2005
Externally publishedYes

Keywords

  • Costimulation
  • Human
  • Inflammation
  • Renal tubular epithelial cells

ASJC Scopus subject areas

  • Nephrology

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