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

Abstract

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.

• Authors: Patricia Wahl, Roland Schoop, Grozdana Bilic, Jörg Neuweiler, Michel Le Hir, Steven K Yoshinaga, Rudolf P Wüthrich
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 13 Issue 6 Pg. 1517-26 (Jun 2002) ISSN: 1046-6673 [Print] United States
• PMID: 12039981 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• B7-1 Antigen
• B7-2 Antigen
• CD40 Antigens
• CD86 protein, human
• Cd86 protein, mouse
• ICOS protein, human
• Icos protein, mouse
• Inducible T-Cell Co-Stimulator Ligand
• Inducible T-Cell Co-Stimulator Protein
• Membrane Glycoproteins
• RNA, Messenger

Topics

• Animals
• Antigen Presentation
• Antigens, CD (analysis, genetics)
• Antigens, Differentiation, T-Lymphocyte (physiology)
• B7-1 Antigen (analysis, genetics, physiology)
• B7-2 Antigen
• CD40 Antigens (analysis, genetics)
• Cell Line
• Epithelial Cells (chemistry)
• Humans
• Immunohistochemistry
• Inducible T-Cell Co-Stimulator Ligand
• Inducible T-Cell Co-Stimulator Protein
• Kidney Tubules (chemistry)
• Membrane Glycoproteins (analysis, genetics)
• Mice
• Mice, Inbred C57BL
• RNA, Messenger (analysis)