Murine Systemic Autoimmune Disease Induced by Mercuric Chloride: T Helper Cells Reacting to Self Proteins

Abstract

HgCl₂ induces a CD4+ T-cell-dependent systemic autoimmune disease in susceptible strains of rats and mice. In rats, autoreactive T cells were shown to be involved, whereas in mice, attention has focussed on the demonstration of ‘Hg-specific’ T cells. To clarify these seemingly different T cell involvements, T cells from B10.S mice treated with HgCl₂ for 1 or 8 weeks were analyzed for their capacity to mount anamnestic responses against various self antigens (Ags) which either contained Hg or did not. T cells from donors short-term treated with HgCl₂ failed to mount memory responses to Hg-free Ags, but mounted a significant response to HgCl₂ and also reacted with Hg-containing self Ags. Interestingly, T cells from donors long-term treated with HgCl₂ showed a different pattern of reactivity. They hardly reacted to HgCl₂ and reacted poorly to Hg-containing splenic proteins, but responded vigorously to nuclei and fibrillarin irrespective of whether these self constituents had been treated with HgCl₂ or not. Conceivably, the initial activation of T cells that recognize Hg in combination with nuclear self proteins, such as fibrillarin, eventually results in activation of T cells specific for the unaltered self proteins.

Infectious Nickel Tolerance: A Reciprocal Interplay of Tolerogenic APCs and T Suppressor Cells That Is Driven by Immunization

“…Previously, we proposed that Ni 2ϩ ions, unlike other sensitizing metal ions (22)(23)(24)(25), would be unable to up-regulate the expression of costimulatory molecules, whereas the administration of NiCl 2 together with H 2 O 2 would induce both signal 1 and signal 2 (17). Here, the validity of this hypothesis has been confirmed.…”

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

“…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. Recently, some progress has been made [39,40], in that bulk T cells of HgCl 2 -treated B10.S mice were found to react against a variety of different self proteins altered by Hg 2+ , in particular fibrillarin, a small ribonucleoprotein that is mainly located in the nucleolus and is the principal target of ANolA in these mice [41,42]. Moreover, in HgCl 2 -treated Brown Norway rats an activation of autoreactive CD4 + T cells has been described [43,44], albeit that the MHC II-associated self proteins recognized by them have not yet been identified; recent experimental evidence indicates that these cells are of the Th2 type [17] (P. Druet, personal communication).…”

Immunological effects of mercury (IUPAC Technical Report)

“…Shifts in the ratios of lymphocyte subpopulations have also been observed in rodents [41]. Although B-lymphocytes and their autoantibody-products are of major importance in the autoimmune process, there is some evidence that active T-lymphocytes, and possibly suppressor-cells, are also involved [33,[42][43][44].…”

“…T-lymphocytes from donor mice treated for a week with subcutaneous injections of mercury(II) chloride were tested in a popliteal lymph node assay. Cells mounted a response to mercury(II) chloride and to splenic proteins isolated from mercury-treated mice [33]. The latter proteins contained mercury.…”