Development of immune-complex glomerulonephritis in athymic mice: T cells are not required for the genesis of glomerular injury.
Chronic injection of dextran into normal mice elicits a glomerulonephritis (GN) that models IgA nephropathy (IgAN) in humans. Since athymic mice lack T cells but nonetheless develop antibodies to polysaccharide antigens such as dextran (DEX), we used athymic mice to study the role of T lymphocytes in the induction of this form of GN, independent of the role of T cells in antibody synthesis. Both mice given injections of diethylaminoethyl (DEAE)-DEX and uninjected mice had circulating IgM and IgA anti-DEX antibodies, which apparently arise as 'natural antibodies', but immune complex GN was observed only in the injected mice. All of 15 injected mice exhibited capillary staining for IgA and IgM; none of 12 control mice contained such IgA deposits and only one had capillary staining for IgM (both P<0.001). In addition, IgG and C3 were detected in injected but not control animals. By light microscopy, injected mice exhibited marked expansion of mesangial matrix relative to controls. Electron microscopy showed no glomerular abnormalities in control mice, whereas injected mice showed large organized fibrillar deposits principally in the mesangium. Hematuria and proteinuria were present in all 15 injected mice, but only one of 11 control mice showed hematuria or proteinuria (both P<0.001). These results indicate that chronic injection of DEAE-DEX into athymic mice generates the same clinical and histologic features of GN as in euthymic mice, suggesting that T cells are not necessary to promote GN in this model.
Bagheri
Nayer
N
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Pepple
Douglas A
DA
Hassan
Medhat O
MO
Harding
Clifford V
CV
Emancipator
Steven N
SN
D000818:Animals; D003911:Dextrans; D004983:Ethanolamines; D005920:Glomerular Mesangium / Q000276:immunology* / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D006417:Hematuria / Q000503:physiopathology; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude / Q000276:immunology*; D046529:Microscopy, Electron, Transmission; D011507:Proteinuria / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D003911:Dextrans; D004983:Ethanolamines; D007070:Immunoglobulin A; D007075:Immunoglobulin M; C007369:2-diethylaminoethanol