Renal tubular epithelial expression of the costimulatory molecule B7RP-1 (inducible costimulator ligand)

MHC class II-expressing renal tubular epithelial cells (TEC) are able to present foreign peptide antigens to T cells. The costimulatory signals that are required for effective T cell activation upon antigen presentation by TEC have not been characterized. Various cultured TEC lines were examined for...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2002-06, Vol.13 (6), p.1517-1526
Main Authors: WAHL, Patricia, SCHOOP, Roland, BILIC, Grozdana, NEUWEILER, Jörg, LE HIR, Michel, YOSHINAGA, Steven K, WÜTHRICH, Rudolf P
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens, CD - analysis
Antigens, CD - genetics
Antigens, Differentiation, T-Lymphocyte - physiology
B7-1 Antigen - analysis
B7-1 Antigen - genetics
B7-1 Antigen - physiology
B7-2 Antigen
Biological and medical sciences
CD40 Antigens - analysis
CD40 Antigens - genetics
Cell Line
Epithelial Cells - chemistry
Fundamental and applied biological sciences. Psychology
Humans
Immunohistochemistry
Inducible T-Cell Co-Stimulator Ligand
Inducible T-Cell Co-Stimulator Protein
Kidney Tubules - chemistry
Membrane Glycoproteins - analysis
Membrane Glycoproteins - genetics
Mice
Mice, Inbred C57BL
RNA, Messenger - analysis
Vertebrates: urinary system
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Summary:MHC class II-expressing renal tubular epithelial cells (TEC) are able to present foreign peptide antigens to T cells. The costimulatory signals that are required for effective T cell activation upon antigen presentation by TEC have not been characterized. Various cultured TEC lines were examined for expression of the recently described costimulatory molecule B7RP-1 (B7h), a ligand of the T cell molecule inducible costimulator (ICOS), and expression was compared with that of B7.1, B7.2, and CD40. B7RP-1 and CD40 were abundantly expressed by cultured murine and human TEC, whereas B7.1 and B7.2 could not be detected. Stimulation with lipopolysaccharide or tumor necrosis factor-alpha did not induce B7.1 or B7.2 expression and did not alter B7RP-1 expression. Interestingly, interleukin-2 production by T cell hybridomas after antigen presentation by TEC was enhanced by blocking antibodies to B7RP-1 and ICOS. In contrast, blocking antibodies to B7RP-1 or ICOS exerted inhibitory effects on anti-CD3-activated murine splenocyte proliferation. Immunohistochemical staining of normal human kidneys demonstrated strong constitutive B7RP-1 expression in distal tubules, collecting ducts, and urothelium. In human kidneys with allograft rejection or interstitial nephritis, distinct B7RP-1 staining was also detected in proximal tubules, in areas of mononuclear infiltration. In conclusion, the B7RP-1/ICOS pathway negatively regulates T cell activation upon MHC class II-restricted antigen presentation by TEC. Because B7RP-1 is also expressed by tubules in vivo, it can be speculated that the B7RP-1/ICOS pathway could play an inhibitory role in TEC-mediated immune activation in the kidney.
ISSN:1046-6673
1533-3450
DOI:10.1097/01.asn.0000017901.77985f