Delivering PD-1 inhibitory signal concomitant with blocking ICOS co-stimulation suppresses lupus-like syndrome in autoimmune BXSB mice

BXSB mice spontaneously develop an autoimmune syndrome characterized by hypergammaglobulinemia, autoantibody production, and the development of fatal glomerulonephritis that closely resembles systemic lupus erythematosus (SLE) in humans. While blocking positive T cell co-stimulation has shown effect...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 118(2006), 2-3 vom: 02. Feb., Seite 258-67
1. Verfasser: Ding, Hanlu (VerfasserIn)
Weitere Verfasser: Wu, Xiongfei, Wu, Jun, Yagita, Hideo, He, Yani, Zhang, Jianguo, Ren, Jiangwen, Gao, Wenda
Format: Aufsatz
Sprache:English
Veröffentlicht: 2006
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Antigens, Differentiation Antigens, Differentiation, T-Lymphocyte ICOS protein, human Icos protein, mouse Icosl protein, mouse Immunoglobulin G Inducible T-Cell Co-Stimulator Ligand Inducible T-Cell Co-Stimulator Protein mehr... Pdcd1 protein, mouse Programmed Cell Death 1 Receptor Proteins DNA 9007-49-2
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245 1 0 |a Delivering PD-1 inhibitory signal concomitant with blocking ICOS co-stimulation suppresses lupus-like syndrome in autoimmune BXSB mice 
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520 |a BXSB mice spontaneously develop an autoimmune syndrome characterized by hypergammaglobulinemia, autoantibody production, and the development of fatal glomerulonephritis that closely resembles systemic lupus erythematosus (SLE) in humans. While blocking positive T cell co-stimulation has shown effectiveness in preventing the onset of murine lupus, deliberate delivering negative co-stimulation to halt unwanted T and B cell activation has not been tested. We developed a recombinant adenovirus containing the full-length mouse PD-L1 gene (Ad.PD-L1) to engage the immunoinhibitory receptor PD-1 on activated lymphocytes to prevent lupus nephritis in BXSB mice. This strategy was further reinforced by concomitant injection of anti-ICOSL(B7h) mAb to block ICOS-mediated co-stimulation. The combined therapy dramatically delayed the onset of proteinuria, effectively inhibited IgG autoantibody production, and significantly reduced hypercellularity and deposition of IgG in glomeruli, resulting in almost complete amelioration of lupus nephritis in these animals. Our results indicate the therapeutic potential of simultaneous stimulation of PD-1-mediated pathway and blockade of ICOS-B7h co-stimulation in the prevention of human lupus nephritis 
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700 1 |a Wu, Xiongfei  |e verfasserin  |4 aut 
700 1 |a Wu, Jun  |e verfasserin  |4 aut 
700 1 |a Yagita, Hideo  |e verfasserin  |4 aut 
700 1 |a He, Yani  |e verfasserin  |4 aut 
700 1 |a Zhang, Jianguo  |e verfasserin  |4 aut 
700 1 |a Ren, Jiangwen  |e verfasserin  |4 aut 
700 1 |a Gao, Wenda  |e verfasserin  |4 aut 
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