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.