Immunoregulation of mercuric chloride-induced autoimmunity in Brown Norway rats: a role for CD8+ T cells revealed by in vivo depletion studies.
Mercuric chloride (HgCl2) induces the production of autoantibodies to glomerular basement membrane (GBM) in the Brown Norway (BN) rat. The autoimmune response is self-limiting and thereafter the animals are resistant to rechallenge with HgCl2. Resistance can be transferred to naive animals by spleen cells from HgCl2-treated rats. A similar state of resistance can be induced with a low dose of HgCl2, insufficient in itself to induce autoimmunity. We have examined the role of CD8+ T cells in the immunoregulation of this experimental model by depleting this subset in vivo. We have also used inhibition studies in a solid-phase radioimmunoassay in an attempt to demonstrate any effect of anti-idiotypic antibodies in the spontaneous resolution of the anti-GBM antibody response. The initial induction and spontaneous resolution of anti-GBM antibodies were unaffected by depletion of CD8+ T cells. However, CD8-depleted animals were no longer resistant to rechallenge with HgCl2. Cell transfer studies showed that spleen cells from CD8-depleted animals conferred less resistance to HgCl2 than those from animals which had received control antibody. CD8 depletion also reduced the resistance induced by pretreatment with low-dose HgCl2. Studies in which peak sera were pre-incubated with post-recovery sera before testing in a solid-phase anti-GBM radioimmunoassay did not support an important role for anti-idiotypic antibodies. We conclude that CD8+ T cells play an important role in the resistance to rechallenge with HgCl2 in the BN rat, although they are not required for the induction or spontaneous resolution of the initial autoimmune response. Demonstration of the reversal of a suppressive phenomenon in vivo using an anti-CD8 monoclonal antibody is unusual.
Mathieson
P W
PW
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, GB.
Stapleton
K J
KJ
Oliveira
D B
DB
Lockwood
C M
CM
D000704:Analysis of Variance; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte; D015551:Autoimmunity / Q000502:physiology*; D001485:Basement Membrane / Q000276:immunology; D016827:CD8 Antigens; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance; D007678:Kidney Glomerulus / Q000276:immunology*; D008297:Male; D008627:Mercuric Chloride; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D008627:Mercuric Chloride