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. The aim of this work was to investigate, using T cell lines derived from HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW × BN)F1 hybrids. The lines produce, in addition to IL-2, IFN-γ and TGF-β, and the protective effect is TGF-β dependent since protection is abrogated by anti-TGF-β treatment. These results identify regulatory, TGF-β–producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.

Mercuric chloride induces anti-glomerular basement membrane antibodies in the Brown-Norway rat. Various other inbred rat strains (Lewis, Wistar AG, August, PVG/c) were not found to be able to produce such antibodies under the same experimental conditions. Hybrids (F1, F2 and F1 x LEW) were bred from Brown-Norway and Lewis rats and injected with mercuric chloride. It has been demonstrated that the induction of anti-glomerular basement membrane antibodies by mercuric chloride in these crosses is under genetic control. The response was found to depend on two or three genes one of which was H-1-linked. The negative results obtained with L.BN congenic rats were in complete agreement with this conclusion.