Mercuric chloride-induced autoimmunity.

This unit describes methods for inducing autoimmune disease in Brown Norway rats through HgCl(2) injections as well for assessing parameters that characterize the disease by serum IgE concentration assays, anti-laminin antibody measurement, and renal immunofluorescence studies to detect autoantibodies. Also covered are disease induction using autoreactive CD4(+) T(H)2 anti-self MHC class II molecules and preparation of T cell lines. IL-4 is produced very early after the first HgCl(2) injection (beginning at day 3, peaking at day 14, and continuing up to day 30).

Identification of mu-opioid receptor epitopes recognized by agonistic IgG.

We have previously reported the presence of IgG antibodies with a morphine-like activity in the serum of healthy individuals. The agonistic activity of IgG was dependent on their binding to the first and the third extracellular loops of the human mu opioid receptor. In this study we show that IgG antibodies obtained by immunizing rats with peptides corresponding to these two loops exhibited a similar morphine-like activity.

Non-immunoglobulin serum proteins prevent the binding of IgG from normal rats and from rats with Th2-mediated autoimmune glomerulonephritis to various autoantigens including glomerular antigens.

It is now well established in normal humans and mice that purification of IgG from serum unmasks their autoantibody activity. Mercuric chloride (HgCl2) induces in Brown-Norway (BN) rats a Th2-dependent polyclonal B cell activation, a huge increase in serum IgE and IgG1 concentrations, the production of numerous autoantibodies and an autoantibody-mediated glomerulonephritis. In the present study we have compared the IgG autoantibody activity in the serum and in the purified IgG fraction from normal and HgCl2-injected BN rats.

Transforming growth factor beta (TGF-beta)-dependent inhibition of T helper cell 2 (Th2)-induced autoimmunity by self-major histocompatibility complex (MHC) class II-specific, regulatory CD4(+) T cell lines.

Autoreactive anti-MHC class II T cells are found in Brown Norway (BN) and Lewis (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease.

Characteristics of polyreactive and monospecific IgG anti-laminin autoantibodies in the rat mercury model.

Brown-Norway (BN) rats injected with HgCl2 produce anti-laminin antibodies responsible for an autoimmune glomerulonephritis. The properties of three IgG1 monoclonal antibodies (mAb) previously obtained in this model, and of immunoglobulins eluted from kidneys of diseased rats, were compared in the present study. Two mAb (Hg15 and Hg16) recognized laminin only, while the third one (Hg17) was polyreactive, as were some of the kidney-eluted immunoglobulins; they reacted with laminin and with several other antigens including 2,4,6-trinitrophenyl (TNP).