Renal tubular epithelial expression of the costimulatory molecule B7RP 1 ( inducible costimulator ligand ). (2002 May)
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 …

CD28 B7 blockade prevents the development of experimental autoimmune glomerulonephritis. (2000 Mar)
CD28 B7 blockade prevents the development of experimental autoimmune glomerulonephritis . experimental autoimmune glomerulonephritis ( EAG ) , an animal model of goodpasture s disease , can be induced in wistar kyoto ( WKY ) rats by a single injection of rat glomerular basement membrane ( GBM ) in adjuvant . EAG is characterized by circulating and deposited anti GBM antibodies , accompanied by focal necrotizing glomerulonephritis with crescent formation . The role of T cells in the pathogenesis of EAG remains unclear . T cell costimulation is provided by ligation of CD28 with either B7 . 1 ( CD80 ) or B7 . 2 ( CD86 ) on antigen presenting cells , and can be inhibited by a soluble form of ctla4 ( ctla4 Ig ) that binds to both B7 . 1 and B7 . 2 . We examined the effect of CD28 B7 blockade on the development of EAG using native ctla4 Ig or mutant ctla4 Ig ( y100f Ig ) , which selectively blocks B7 . 1 . native ctla4 Ig treatment ameliorated EAG by several measures , including the levels of circulating anti GBM antibodies , albuminuria , the deposition of IgG and fibrin in the glomeruli , the severity of glomerular abnormalities , and the numbers of infiltrating T cells and macrophages . y100f Ig resulted in a similar reduction in the severity of nephritis , but produced no overall reduction in circulating anti GBM antibodies , although there was a reduction in igg2a …

Costimulation by B7 1 and B7 2 is required for autoimmune disease in MRL faslpr mice. (2000 Jun)
costimulation by B7 1 and B7 2 is required for autoimmune disease in MRL faslpr mice . autoimmune lupus nephritis is dependent on infiltrating autoreactive leukocytes and Igs . B7 costimulatory molecules ( B7 1 and B7 2 ) provide signals essential for T cell activation and Ig class switching . In MRL faslpr mice , a model of human lupus , although multiple tissues are targeted for autoimmune injury , nephritis is fatal . We identified intrarenal B7 1 and B7 2 expression , restricted to kidney infiltrating leukocytes , before and increasing with progressive nephritis in MRL faslpr mice . Thus , we hypothesized that the B7 pathway is required for autoimmune disease in MRL faslpr mice . To investigate the role of B7 costimulatory molecules in this autoimmune disease , we generated a MRL faslpr strain deficient in B7 1 and B7 2 . strikingly , MRL faslpr mice lacking both B7 costimulators do not develop kidney ( glomerular , tubular , interstitial , vascular ) pathology , or proteinuria , and survive far longer . intrarenal downstream effector transcripts ( IFN gamma , IL 12 , monocyte chemoattractant protein 1 , CSF 1 ) linked to nephritis remained at normal levels compared with wild type mice . Skin lesions and lymphoid enlargement characteristic of MRL faslpr mice were diminished in B7 1 / B7 2 deficient MRL faslpr mice . B7 1 / B7 2 deficient MRL faslpr mice did not develop leukocytic infiltrates , elevated …

Renal tubular epithelial expression of the coinhibitory molecule B7 DC ( programmed death 1 ligand ). (2006 Oct)
renal tubular epithelial expression of the coinhibitory molecule B7 DC ( programmed death 1 ligand ) . background : renal tubular epithelial cells ( TECs ) function as antigen presenting cells because they constitutively express MHC class II molecules and have the ability to present peptide antigen to CD4 T cells . however , the costimulatory signals provided by TECs for optimal T cell activation have not been fully characterized . increasing recognition of the importance of B7 dendritic cells ( B7 DC ) in immunoregulation raises the question of whether B7 DC is expressed on TECs and is involved in regulating TEC function . methods : B7 DC on cultured human and murine TECs was detected by flow cytometry in vitro . immunohistochemistry was performed on human kidney biopsies . coculture experiments were performed to confirm the role of TEC related B7 DC in regulating CD4 T cell activation . results : Data revealed that B7 DC is specifically expressed on TECs with inflammatory factor induced and diseased human kidney samples , including chronic glomerulonephritis , lupus nephritis , tubulointerstitial nephritis and renal cell carcinoma . B7 DC was a strong inhibitor of CD4 T cell activation , as assessed by increased cytokine ( interferon gamma and interleukin 2 ) production and enhanced levels of T cell activation marker CD69 in the presence of its blocking antibody . blocking B7 DC / PD 1 enhanced antigen presentation . B7 DC is especially well expressed on TECs of diseased kidney …

Expression of the novel co stimulatory molecule B7 H4 by renal tubular epithelial cells. (2006 Nov)
expression of the novel co stimulatory molecule B7 H4 by renal tubular epithelial cells . crosstalk between T cells and renal tubular epithelial cells ( TECs ) in the pathogenesis of tubular lesions , the most important sign of progressive renal diseases , has not been clarified . previous work has shown that TECs harbor co stimulatory signals that promote T cell activation , which induces tubular lesions . nevertheless , the expression and functional role of B7 H4 , a recently identified co stimulatory ligand of the B7 superfamily , in pathologic human kidneys is unclear . We investigated the expression of B7 H4 on cryostat renal biopsies from patients with idiopathic membranous nephropathy ( n 20 ) , immunoglobulin A nephropathy ( n 19 ) , lupus nephritis ( n 16 ) , and acute renal allograft rejection ( n 15 ) using immunohistochemistry . In addition , we also analyzed TEC associated B7 H4 in the regulation of T cell activation . immunohistological staining revealed that B7 H4 antigen is restricted to tubular epithelium and that the protein is prominent in sections with severe tubular lesions , although no correlation was observed between tubular B7 H4 expression and levels of serum creatinine , serum urea nitrogen concentration , and 24 h proteinuria in each type of nephropathy . In vitro , mixed lymphocyte reactions revealed that TEC related B7 H4 promotes cytokine ( interleukin 2 and interferon gamma ) production and proliferation of co cultured T cells …

Involvement of inducible costimulator B7 homologous protein costimulatory pathway in murine lupus nephritis. (2003 Sep)
involvement of inducible costimulator B7 homologous protein costimulatory pathway in murine lupus nephritis . inducible costimulator ( ICOS ) B7 homologous protein ( B7h ) is a new member of the CD28 B7 family of costimulatory molecules that regulates T cell dependent humoral immune responses . In this study , we examined the involvement of this costimulatory pathway in the development and progression of lupus in NZB / W F ( 1 ) mice . expression of ICOS on T cells was enhanced with disease progression , whereas B7h expression on B cells was down regulated . administration of anti B7h mAb before the onset of renal disease significantly delayed the onset of proteinuria and prolonged survival . blockade of B7h effectively inhibited all subclasses of IgG autoantibody production and accumulation of both Th1 and Th2 cells . hypercellularity and deposition of IgG and C3 in glomeruli were significantly reduced . B7h blockade after the onset of proteinuria prevented the disease progression and improved the renal pathology . Our results demonstrated the involvement of the ICOS B7h costimulatory pathway in the pathogenesis of lupus nephritis , and the blockade of this pathway may be beneficial for the treatment of human systemic lupus erythematosus .