Resistance to re-challenge in the Brown Norway rat model of vasculitis is not always complete and may reveal separate effector and regulatory populations.
Administration of mercuric chloride to Brown Norway rats results in T helper type 2 (Th2)- dominated autoimmunity characterized by high immunoglobulin E (IgE) concentrations, the production of multiple IgG autoantibodies, including those to glomerular basement membrane (GBM), arthritis and caecal vasculitis. After 14 days animals immunoregulate and auto-immunity resolves even if mercuric chloride injections are continued. In a third phase, if animals are re-challenged with mercuric chloride 6 weeks later, they show only attenuated autoimmunity with lower anti-GBM antibody concentrations and arthritis scores. Resistance to the induction of anti-GBM antibodies can also be achieved following an initial challenge with low-dose (one-tenth standard dose) mercuric chloride. We have now studied this resistant phase in more detail. We have shown, first, that following an initial full-dose mercuric chloride challenge, resistance also affects susceptibility to caecal vasculitis. Second, following an initial full-dose mercuric chloride challenge, the IgE response upon re-challenge is initially accelerated but subsequently enters a resistant phase and third, following an initial challenge with low-dose mercuric chloride, resistance is also seen to the induction of caecal vasculitis but is not seen in IgE serology (where results suggest competing effector and regulatory cell populations). Studying such regulatory phases in animal models of autoimmunity may be of benefit in the future in designing new therapies for human vasculitis.
Vinen
C S
CS
Department of Renal Medicine, St George's Hospital Medical School, Cranmer Terrace, London, UK.
Turner
D R
DR
Oliveira
D B G
DB
D000818:Animals; D001168:Arthritis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D002429:Cecal Diseases / Q000276:immunology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D007073:Immunoglobulin E / Q000032:analysis; D008297:Male; D008627:Mercuric Chloride / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D018418:Th2 Cells; D014657:Vasculitis / Q000276:immunology*
D007073:Immunoglobulin E; D008627:Mercuric Chloride