Mercury-induced autoimmunity in the absence of IL-4.
In susceptible H-2S mice, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by production of anti-nucleolar antibodies (ANoA) and increased serum levels of IgG1 and IgE antibodies. The increase in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in the induction of this syndrome. We have previously shown that administration of IL-12, a potent Th1-promoting cytokine, resulted in a dramatic reduction of the HgCl2-induced anti-nucleolar antibody titres and inhibited serum IgG1 increase. These results suggest that Th1 T cells can down-regulate ANoA, and support a role for the Th2 subset in ANoA production, possibly via IL-4. To examine the role of IL-4 in this syndrome, C57Bl/6 mice (H-2b) with a targeted deletion of the IL-4 gene were mated with A.SW mice (H-2S) to yield H-2S mice lacking IL-4. We then analysed ANoA and serum immunoglobulin levels in these mice after HgCl2 treatment. While mercury-treated IL-4(-/-) H-2S mice had virtually no detectable serum IgG1 or IgE, and very low levels of IgG1 ANoA, these mice had levels of IgG2a and IgG2b class ANoA comparable to mercury-treated IL-4+ H-2S mice, indicating that IL-4 is not required for the ANoA response in mercury-induced autoimmunity.
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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LM
Bagenstose
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Salgame
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Monestier
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013577:Syndrome
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride