Mechanism of mercury-induced autoimmunity: both T helper 1- and T helper 2-type responses are involved.
Mercury can induce a systemic autoimmune disease in susceptible mouse strains. H-2s mice are particularly susceptible to mercury-induced autoimmunity and other mouse strains are more or less resistant. T helper 1/T helper 2 (Th1/Th2) dichotomy has been proposed for resistance or susceptibility, respectively. In the current study we show that mercury treatment induced a full autoimmune response in both C57BL/6 (H-2b) wild-type and interleukin-4 (IL-4)-deficient mice. Antibody production of all isotypes were induced, except that in IL-4-deficient mice there was no immunoglobulin E (IgE) and very low levels of immunoglobulin G1 (IgG1) antibody synthesis. Autoantibodies of different specificities were produced. The granular pattern of all IgG subclasses deposits were detected in the kidneys. In contrast to mercury-treated H-2s seconds mice, we did not detect any anti-nucleolar autoantibodies in the sera of mercury-treated wild-type or IL-4-deficient mice. To further explore the role of Th1/Th2 cytokines in the mercury model, we performed anti-interferon-gamma antibody treatment in IL-4-deficient mice together with mercury treatment and found that the production of IgG2a and IgG3, but not IgG2b, antibodies was downregulated. This indicated that besides Th2-type cytokines, Th1-type and other cytokines were involved as well in mercury-induced autoimmune response. Thus, C57BL/6 mice with H-2b genotype are highly susceptible to mercury-induced autoimmunity, and the genetic susceptibility to mercury involves more than a predisposition of a Th1-or Th2-type response.
Hu
H
H
Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden.
Möller
G
G
Abedi-Valugerdi
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D019085:Fluorescent Antibody Technique, Direct; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007668:Kidney / Q000276:immunology; D008628:Mercury / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D015847:Interleukin-4; D007371:Interferon-gamma; D008628:Mercury