Article: article from journal or magazin.
Inhibition of the CD40-CD40ligand pathway prevents murine membranous glomerulonephritis
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Several forms of glomerulonephritis are induced by antibodies against self or foreign antigens. Normal B lymphocyte antibody production requires T cell costimulatory signals provided in part by T cell surface expression of gp39/CD40ligand (CD40L) that engages the B cell receptor CD40 and induces B cell differentiation and immunoglobulin class switching. We assessed the effect of disrupting the CD40L-CD40 costimulatory pathway, using a CD40-Ig fusion protein, on the development of membranous glomerulonephritis (MGN) in the mouse. MGN is induced by mouse antibodies that recognize and bind to exogenously administered rabbit anti-mouse renal tubular brush border (RbAMBB) IgG immobilized in the glomerular capillary wall. MGN did not occur in nude mice, showing the need of the T cell function. C57Bl/10 mice immunized with RbAMBB and treated with CD40-Ig fusion protein displayed a delayed autologous response and absence of MGN lesions, while control fusion proteins failed to prevent the development of the disease. These observations provide evidence that disruption of the CD40-CD40L costimulatory pathway can prevent the development of MGN by suppressing T cell-dependent antibody production
Animals/Antibodies,Monoclonal/Antigens,CD40/genetics/metabolism/Base Sequence/Fluorescent Antibody Technique/Glomerulonephritis,Membranous/Pathology/prevention & control/Immunoglobulins/Kidney Glomerulus/Ligands/Male/Mice/Mice,Inbred C57BL/Microscopy,Electron/Molecular Probes/Molecular Sequence Data/Rabbits/Recombinant Fusion Proteins/pharmacology/Solubility/Research
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