Prevention of adjuvant arthritis in Lewis rats by neonatal bacille Calmette-Guerin (BCG) infection.
Tolerization of pathogenic antigens is one of the experimental strategies that has been proposed to prevent autoimmune disease. We have investigated here whether neonatal intraperitoneal infection of Lewis rats with Mycobacterium bovis-BCG has any effect on the expression of adjuvant arthritis (AA), an autoimmune disease that is produced by immunization of the rats with dead mycobacteria in mineral oil (i.e. Freund's complete adjuvant (FCA)). We found that neonatal infection with 10(8) viable BCG bacilli rendered all Lewis rats resistant to the expression of AA after FCA immunization. This BCG-induced protection from reactive arthritis was not seen in Lewis rats infected with smaller inocula (10(6) BG bacilli) or if the infection was performed after the neonatal period (e.g. at 3 weeks of age). Neonatal administration of 65-kD mycobacterial heat shock protein (hsp65, a key antigen in the etiopathogenesis of AA) failed to protect Lewis rats from AA; injection of lactoferrin (an autoantigen that may be involved in the physiopathology of autoimmune arthritis) to newborn Lewis rats decreased the severity of AA observed after FCA immunization of the animals. Western blotting revealed that Lewis rats that had acquired resistance to AA also showed changes in their repertoire of antibody specificities; among these alterations was decreased anti-hsp65 reactivity. We conclude that neonatal infection with BCG, but not hsp65 injection, renders Lewis rats resistant to AA and that the phenomenon is associated with change in the repertoire of specificities of circulating antibodies.
Esaguy
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Centre for Experimental Cytology, University of Porto, Portugal.
Aguas
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D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001428:Bacterial Vaccines; D005260:Female; D007108:Immune Tolerance; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
D001428:Bacterial Vaccines