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- Title
Renal tubular epithelial cells modulate T-cell responses via ICOS-L and B7-H1.
- Authors
de Haij, Simone; Woltman, Andrea M.; Trouw, Leendert A.; Bakker, Astrid C.; Kamerling, Sylvia W.; van der Kooij, Sandra W.; Lieping Chen; Kroczek, Richard A.; Daha, Mohamed R.; van Kooten, Cees
- 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.
- Subjects
RENAL tubular transport; EPITHELIAL cells; INFLAMMATION; T-cell receptor genes; IMMUNOCHEMISTRY; BIOPSY; IMMUNOGLOBULINS
- Publication
Kidney International, 2005, Vol 68, Issue 5, p2091
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1111/j.1523-1755.2005.00665.x