scholarly journals CD4+ T cells specific to a glomerular basement membrane antigen mediate glomerulonephritis

2002 ◽  
Vol 109 (4) ◽  
pp. 517-524 ◽  
Author(s):  
Jean Wu ◽  
John Hicks ◽  
Jason Borillo ◽  
William F. Glass ◽  
Ya-Huan Lou
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Cd4 T Cells ◽  
Basement Membrane Antigen

scholarly journals Th2 responses induce humorally mediated injury in experimental anti-glomerular basement membrane glomerulonephritis.

1997 ◽  
Vol 8 (7) ◽  
pp. 1101-1108 ◽  
Author(s):  
X R Huang ◽  
S R Holdsworth ◽  
P G Tipping
Keyword(s):  
T Cells ◽  
T Cell ◽  
Basement Membrane ◽  
Immune Responses ◽  
Glomerular Basement Membrane ◽  
Acute Injury ◽  
Delayed Type Hypersensitivity ◽  
Acute Glomerulonephritis ◽  
Neutrophil Influx ◽  
Mouse Immunoglobulin

Acute autologous phase anti-glomerular basement membrane glomerulonephritis was compared in Th1-prone (C57BL/6) and Th2-prone (BALB/c) mice. Sensitized BALB/c mice, given a subnephritogenic intravenous dose of anti-mouse glomerular basement membrane globulin, developed acute glomerulonephritis characterized by marked proteinuria and glomerular deposition of mouse immunoglobulin and complement. A significant glomerular neutrophil influx was observed, but few T cells and macrophages were present. C57BL/6 mice, given the same dose of disease-inducing globulin, also developed acute glomerulonephritis, although their proteinuria was significantly less. Glomerular deposition of mouse immunoglobulin and complement and the influx of neutrophils were also significantly less than in BALB/c mice. However, their glomerular accumulation of macrophages and T cells was significantly greater. Complement depletion attenuated neutrophil influx and proteinuria in BALB/c mice but did not affect T cell or macrophage accumulation or proteinuria in C57BL/6 mice. CD4+ T cell depletion significantly reduced glomerular macrophage, T cell influx, and proteinuria in C57BL/6 mice, but had no effect on proteinuria or neutrophil influx in BALB/c mice. Thus, immune responses to planted glomerular antigens in Th2-prone mice induce acute injury as a result of antibody deposition, complement activation, and neutrophil influx, whereas immune responses to the same antigen in Th1-prone mice induce delayed-type hypersensitivity-like lesions in affected glomeruli.

scholarly journals Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice

2020 ◽  
Vol 21 (19) ◽  
pp. 6978
Author(s):  
Foteini Moschovaki-Filippidou ◽  
Stefanie Steiger ◽  
Georg Lorenz ◽  
Christoph Schmaderer ◽  
Andrea Ribeiro ◽  
...  
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Transforming Growth Factor ◽  
Protective Effects ◽  
Crescent Formation ◽  
Activated T Cells ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Deficient Mice

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.

scholarly journals Voltage-gated potassium channel Kv1.3 blocker as a potential treatment for rat anti-glomerular basement membrane glomerulonephritis

2010 ◽  
Vol 299 (6) ◽  
pp. F1258-F1269 ◽  
Author(s):  
Toshitake Hyodo ◽  
Takashi Oda ◽  
Yuichi Kikuchi ◽  
Keishi Higashi ◽  
Taketoshi Kushiyama ◽  
...  
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Potassium Channel ◽  
Glomerular Basement Membrane ◽  
Memory T Cells ◽  
Critical Role ◽  
Rapidly Progressive Glomerulonephritis ◽  
Effector Memory ◽  
Voltage Gated ◽  
Effector Memory T Cells

The voltage-gated potassium channel Kv1.3 has been recently identified as a molecular target that allows the selective pharmacological suppression of effector memory T cells (TEM) without affecting the function of naïve T cells (TN) and central memory T cells (TCM). We found that Kv1.3 was expressed on glomeruli and some tubules in rats with anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). A flow cytometry analysis using kidney cells revealed that most of the CD4+ T cells and some of the CD8+ T cells had the TEM phenotype (CD45RC−CD62L−). Double immunofluorescence staining using mononuclear cell suspensions isolated from anti-GBM GN kidney showed that Kv1.3 was expressed on T cells and some macrophages. We therefore investigated whether the Kv1.3 blocker Psora-4 can be used to treat anti-GBM GN. Rats that had been given an injection of rabbit anti-rat GBM antibody were also injected with Psora-4 or the vehicle intraperitoneally. Rats given Psora-4 showed less proteinuria and fewer crescentic glomeruli than rats given the vehicle. These results suggest that TEM and some macrophages expressing Kv1.3 channels play a critical role in the pathogenesis of crescentic GN and that Psora-4 will be useful for the treatment of rapidly progressive glomerulonephritis.

Changes in glomerular basement membrane antigen(s) with age

1978 ◽  
Vol 92 (6) ◽  
pp. 952-953 ◽  
Author(s):  
Sudhir K. Anand ◽  
Benjamin H. Landing ◽  
Eva T. Heuser ◽  
David L. Olson ◽  
Carl M. Grushkin ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Basement Membrane Antigen

scholarly journals Oral Administration of Glomerular Basement Membrane Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat

2001 ◽  
Vol 12 (1) ◽  
pp. 61-70
Author(s):  
JOHN REYNOLDS ◽  
CHARLES D. PUSEY
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Oral Administration ◽  
Glomerular Basement Membrane ◽  
Crescent Formation ◽  
Necrotizing Glomerulonephritis ◽  
Wistar Kyoto ◽  
Dose Dependent ◽  
Experimental Autoimmune

Abstract. Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of collagenase-solubilized 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 inhibitory effect of orally administered antigens has been reported in various animal models of autoimmunity but not in EAG in the rat. The effects of feeding rat GBM by gavage, at total doses of 0.5, 2.5, or 5 mg, before immunization were examined. A dose-dependent effect was observed on the development of EAG. A dose of 0.5 mg of GBM had no effect on disease, 2.5 mg resulted in a moderate reduction in the severity of nephritis but no change in anti-GBM antibody production, and 5 mg resulted in a marked reduction in circulating and deposited anti-GBM antibodies, albuminuria, deposits of fibrin in the glomeruli, severity of glomerular abnormalities, and numbers of infiltrating T cells and macrophages. Animals that were fed 5 mg of GBM showed a significant reduction in IgG2a but not IgG1, anti-GBM antibody levels, suggesting downregulation of Th1 responses. There was also a dose-dependent reduction in the proliferative responses of splenic T cells from treated animals to GBM antigen in vitro. These results clearly demonstrate that mucosal tolerance can be induced by oral administration of GBM antigen and that this approach is effective in preventing EAG.

scholarly journals CD4+CD25+ Regulatory T Cells Inhibit Experimental Anti-Glomerular Basement Membrane Glomerulonephritis in Mice

2005 ◽  
Vol 16 (5) ◽  
pp. 1360-1370 ◽  
Author(s):  
Dominik Wolf ◽  
Kathrin Hochegger ◽  
Anna M. Wolf ◽  
Holger F. Rumpold ◽  
Guenther Gastl ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Basement Membrane ◽  
Glomerular Basement Membrane
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