Metal ion induced autoimmunity

Griem, Peter; Gleichmann, Ernst

doi:10.1016/0952-7915(95)80056-5

Cited by 148 publications

(133 citation statements)

References 49 publications

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“…In the rodent models of HgCl 2 -induced immunopathological alterations, however, the precise antigens, let alone the epitopes, that activate CD4 + T cells have not yet been identified [2,38]. Because of this, in vitro demonstration of the CD4 + T cells involved in HgCl 2 -induced immunopathological alterations is difficult and this, in turn, hampered analysis of the cytokines produced by them.…”

Section: Discussionmentioning

confidence: 99%

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

Doth

Fricke

Nicoletti

et al. 1997

Clinical and Experimental Immunology

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SUMMARYUpon treatment with HgCl 2 , H-2 s 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-2 d ) and B10.BR (H-2 k ) mice treated with HgCl 2 , although B10.D2 T cells showed signs of activation by and specificity for HgCl 2 comparable to those seen in strain B10.S. Here, we report that following HgCl 2 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-g. Conversely, treatment of B10.D2 mice with murine recombinant IFN-g (rIFN-g) was able to reproduce the immunosuppression seen after HgCl 2 treatment. In B10.S mice, it took administration of both rIFN-g and HgCl 2 to suppress the antisheep erythrocyte response. Although rIFN-g diminished the increase in IgE serum levels of HgCl 2 -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 HgCl 2 by preferential activation of their Th2 cells producing IL-4, whereas B10.D2 mice react to HgCl 2 by preferential activation of their Th1 cells, which produce IFN-g and thus suppress antibody responses.

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Section: Discussionmentioning

confidence: 99%

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

Doth

Fricke

Nicoletti

et al. 1997

Clinical and Experimental Immunology

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“…Administration of HgCl 2 to Brown Norway (BN) rats induces a T lymphocytedependent systemic autoimmunity, characterized by T and B lymphocyte activation, high production of (auto-)-antibodies, multi-organ inflammation, glomerulonephritis, and proteinuria, which phenotypically resembles systemic lupus erythematosus or chronic graft-versus-host disease [22,23]. The disease has been frequently studied as a model for drug-induced autoimmunity in humans [24]. HgCl 2 preferentially activates Th2 cells in the BN rat, resulting in high production of IL-4 and IgE [25,26].…”

Section: Introductionmentioning

confidence: 99%

Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Roos

Schilder-Tol

Weening

et al. 1998

Journal of Leukocyte Biology

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“…Although public health concerns about mercury exposures have generally focused on neurodevelopmental toxicity, mercury, particularly inorganic mercury (iHg), has been extensively studied in animal models for its immunotoxic properties, which include both autoimmunity and immunosuppression. The autoimmune effects of iHg in susceptible rodent strains include induction of specific autoantibodies, polyclonal activation of T and B cells, increased serum immunoglobulin G1 (IgG1) and IgE, cytokine dysregulation, and an immune complex glomerulonephritis (Bigazzi 1994;Griem and Gleichmann 1995;Mathieson 1992;Moszczynski 1997;Pollard and Hultman 1997).…”

mentioning

confidence: 99%

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

Via

Nguyen

Niculescu

et al. 2003

Environ Health Perspect

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Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.

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Metal ion induced autoimmunity

Cited by 148 publications

References 49 publications

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

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

Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

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