Cyclosporin A induces long-term unresponsiveness in mercuric chloride-induced autoimmune glomerulonephritis.
Mercuric chloride induces a transient systemic T-lymphocyte dependent autoimmune syndrome in Brown Norway rats. Two weeks after the first HgCl2 injection maximum serum levels of anti-GBM antibodies and nephrotic range proteinuria are detected. CyA treatment during HgCl2 administration completely prevented these autoimmune phenomena. Moreover, a prolonged unresponsiveness to HgCl2 was induced, lasting for at least 5 weeks after combined pretreatment with CyA and HgCl2. This unresponsiveness could not be adoptively transferred with peripheral lymphoid cells. Suppression of development of HgCl2-induced proteinuria was adoptively transferred with lymphoid cells from HgCl2-treated donors in remission phase. Unresponsiveness to HgCl2, induced by CyA plus HgCl2 pretreatment, could be broken by reconstitution with naive lymphoid cells. These results suggest that the tolerogenic effect of CyA in HgCl2-induced autoimmunity is not mediated by active suppression; instead, the observed unresponsiveness might be due to direct functional deletion of autoreactive T-lymphocytes. A serendipitous finding was the dissociation in time between synthesis of anti-GBM antibodies and development of proteinuria, suggesting a role for cellular effector mechanisms in the induction of proteinuria.
Aten
J
J
Department of Pathology, University of Leiden, The Netherlands.
Bosman
C B
CB
De Heer
E
E
Hoedemaeker
P J
PJ
Weening
J J
JJ
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000517:prevention & control*; D003524:Cyclosporins / Q000494:pharmacology*; D005921:Glomerulonephritis / Q000139:chemically induced / Q000517:prevention & control*; D007108:Immune Tolerance / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000276:immunology; D017708:Leukocyte Transfusion; D008297:Male; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors*; D051381:Rats; D011914:Rats, Inbred BN
D001323:Autoantibodies; D003524:Cyclosporins; D008627:Mercuric Chloride