Renal tubular epithelial cells modulate T-cell responses via ICOS-L and B7-H1.
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.
de Haij
Simone
S
Department of Nephrology, Leiden University Medical Center, The Netherlands.
Woltman
Andrea M
AM
Trouw
Leendert A
LA
Bakker
Astrid C
AC
Kamerling
Sylvia W
SW
van der Kooij
Sandra W
SW
Chen
Lieping
L
Kroczek
Richard A
RA
Daha
Mohamed R
MR
van Kooten
Cees
C
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
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