Publication

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

Journal Paper/Review - Jun 1, 2002

Units
PubMed

Citation
Wahl P, Schoop R, Bilic G, Neuweiler J, Le Hir M, Yoshinaga S, Wüthrich R. Renal tubular epithelial expression of the costimulatory molecule B7RP-1 (inducible costimulator ligand). Journal of the American Society of Nephrology : JASN 2002; 13:1517-26.
Type
Journal Paper/Review (English)
Journal
Journal of the American Society of Nephrology : JASN 2002; 13
Publication Date
Jun 1, 2002
Issn Print
1046-6673
Pages
1517-26
Brief description/objective

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.