Renal Tubular Epithelial Expression of the Costimulatory Molecule B7RP-1 (Inducible Costimulator Ligand)
| Autor: | Michel Le Hir, Patricia Wahl, Rudolf P. Wüthrich, Roland Schoop, Grozdana Bilic, Steven Kiyoshi Yoshinaga, Jo Rg Neuweiler |
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| Rok vydání: | 2002 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte T cell Antigen presentation Biology Cell Line Inducible T-Cell Co-Stimulator Protein Inducible T-Cell Co-Stimulator Ligand Mice Antigen Antigens CD MHC class I medicine Animals Humans RNA Messenger CD40 Antigens Antigen Presentation Membrane Glycoproteins CD40 Epithelial Cells General Medicine T lymphocyte Immunohistochemistry Cell biology Mice Inbred C57BL Kidney Tubules medicine.anatomical_structure Nephrology Immunology B7-1 Antigen biology.protein B7-2 Antigen |
| Zdroj: | Journal of the American Society of Nephrology. 13:1517-1526 |
| ISSN: | 1533-3450 1046-6673 |
| DOI: | 10.1097/01.asn.0000017901.77985f |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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