Immunoregulation and anti-nuclear antibodies in mercury-induced glomerulopathy in the rat.
The pathogenesis of drug-induced autoimmune antibodies is in most cases uncertain. The recent demonstration of T cell aberrations in human and experimental drug-induced autoimmune disease suggests that immunodysregulation might form the basis of an uncontrolled B cell autoreactivity leading to autoantibody production. In the present study, lymphocytic stimulation by phytohemagglutinin (PHA) and concanavalin A-activated suppressor cell activity was measured in an experimental model of mercury-induced immune complex glomerulopathy associated with anti-nuclear antibodies and vasculitis in PVG/c rats. Both general T cell reactivity to PHA and concanavalin A-activated suppressor function as measured by a syngeneic target cell assay were found to be significantly decreased in mercury-diseased rats as compared with saline-injected control rats. Furthermore, the effect of neonatal and adult thymectomy on the course of the mercury-induced disease was studied. Anti-nuclear antibody activity and glomerular immune aggregate formation were found to be accelerated considerably by neonatal thymectomy, whereas thymectomy at adult age had no significant effect on the interval between the start of mercury administration and the appearance of serological and renal abnormalities. From the results it is concluded that mercury affects both effector and regulatory T cell functions and that immunodysregulation seems to be of pathogenetic significance in this model of drug-induced disease.
D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury; D051381:Rats; D011919:Rats, Inbred Strains; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013934:Thymectomy
D000974:Antibodies, Antinuclear; D008627:Mercuric Chloride; D008628:Mercury