Genetic differences in immune reactivity to mercuric chloride (HgCl2): immunosuppression of H-2d mice is mediated by interferon-gamma (IFN-gamma)

Clin Exp Immunol. 1997 Jul;109(1):149-56. doi: 10.1046/j.1365-2249.1997.4041300.x.

Abstract

Upon treatment with HgCl2, H-2s mice, such as B10.S, develop an activation of B lymphocytes that depends, at least partially, on activation of T helper type 2 (Th2) cells and results in increased serum levels of IgG1 and IgE, appearance of IgG autoantibodies, and development of immune glomerulonephritis and vasculitis. Results of previous studies and of experiments presented here indicate that the B cell activation and systemic autoimmune disease fail to develop in MHC-congenic B10.D2 (H-2d) and B10.BR (H-2k) mice treated with HgCl2, although B10.D2 T cells showed signs of activation by and specificity for HgCl2 comparable to those seen in strain B10.S. Here, we report that following HgCl2 injections the antibody response to sheep erythrocytes is normal in B10.S, but suppressed in B10.D2 mice. This suppression was prevented by MoAb to mouse IFN-gamma. Conversely, treatment of B10.D2 mice with murine recombinant IFN-gamma (rIFN-gamma) was able to reproduce the immunosuppression seen after HgCl2 treatment. In B10.S mice, it took administration of both rIFN-gamma and HgCl2 to suppress the anti-sheep erythrocyte response. Although rIFN-gamma diminished the increase in IgE serum levels of HgCl2-treated B10.S mice, it failed to prevent their autoantibody production and immune glomerulonephritis. These findings further strengthen the concept that B10.S mice react to HgCl2 by preferential activation of their Th2 cells producing IL-4, whereas B10.D2 mice react to HgCl2 by preferential activation of their Th1 cells, which produce IFN-gamma and thus suppress antibody responses.

MeSH terms

  • Animals
  • Antibodies, Antinuclear
  • Antibodies, Blocking / immunology
  • Antibody Formation
  • Autoantibodies / metabolism
  • Erythrocytes / immunology
  • Female
  • Glomerulonephritis / immunology
  • Immunoglobulin E / analysis
  • Immunoglobulin E / blood
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Immunosuppression*
  • Interferon-gamma / genetics*
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Kidney / immunology
  • Mercuric Chloride / immunology*
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Recombinant Proteins / immunology
  • Sheep
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Antibodies, Antinuclear
  • Antibodies, Blocking
  • Autoantibodies
  • Immunoglobulin G
  • Recombinant Proteins
  • Interleukin-4
  • Immunoglobulin E
  • Mercuric Chloride
  • Interferon-gamma