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 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.
Wahl
Patricia
P
Division of Nephrology and Institute of Pathology, Kantonsspital, St. Gallen, Switzerland.
Schoop
Roland
R
Bilic
Grozdana
G
Neuweiler
Jörg
J
Le Hir
Michel
M
Yoshinaga
Steven K
SK
Wüthrich
Rudolf P
RP
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018122:B7-1 Antigen / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis / Q000235:genetics; D002460:Cell Line; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007684:Kidney Tubules / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; C497965:Cd86 protein, mouse; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger