New avian model of experimental glomerulonephritis consistent with mediation by cellular immunity. Nonhumorally mediated glomerulonephritis in chickens.
The present study examined the role of cell-mediated immunity (CMI) in the production of experimental autoimmune glomerulonephritis (EAG) in chickens deficient in humorally mediated immunity (HMI). Cyclophosphamide bursectomized (Bsx) and normal control chickens were used. Bsx chickens were used only if they had severe depression of HMI, which was evidenced by marked reduction in bursal weights (0.89 +/- 0.23 vs. 2.92 +/- 0.9 g), decreased serum IgG to less than or equal to 10% of normal, and total lack of HMI to immunization with sheep red blood cells. EAG was produced by immunizing chickens with bovine glomerular basement membrane (GBM) in complete Freund's adjuvant. CMI manifested by wattle thickness increments to PPD was not different, 3.89 +/- 0.45 mm for Bsx compared with 3.73 +/- 0.75 mm for controls. No circulating antibodies to GBM developed in 68% of Bsx chickens, and the anti-GBM titers were less than 1:312 in those Bsx chickens positive for antibody compared with greater than 2,000 for controls. GBM deposits of IgG by fluorescence were much decreased, 0.53 +/- 0.16 compared with 2.19 +/- 0.32 for controls, and were absent in 64% of Bsx chickens. Nonetheless, proliferative nephritis with crescents was present and was even more severe in Bsx chickens than in controls, with glomerular sizes of 20.8 +/- 0.6 U for Bsx-GBM, 19.8 +/- 1.2 for control-GBM, 14.9 +/- 1.5 for Bsx, and 13.6 +/- 0.8 for normal chickens. Nephritic eluates did not produce disease in normal chickens, while administration of sensitized cells with [H3]thymidine to naive birds was associated with increased mesangial grain counts by autoradiography. These findings suggest that CMI plays a major role in the pathogenesis of EAG in chickens in the absence of HMI. By implication, CMI may be crucial in the development of other types of glomerulonephritis as well.
D000818:Animals; D000917:Antibody Formation; D001835:Body Weight; D002060:Bursa of Fabricius / Q000187:drug effects / Q000473:pathology; D002645:Chickens; D003520:Cyclophosphamide / Q000494:pharmacology; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D008954:Models, Biological
D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D003520:Cyclophosphamide