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From the Institut National de la Sante et de la Recherche Medicale U28, Institut Fédératif de Recherche 30, Université Paul Sabatier, 31059 Toulouse, France

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 x BN)F1 hybrids. The lines produce, in addition to IL-2, IFN- 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.

¹ Abbreviations used in this paper: AU, arbitrary units; BN, Brown Norway; EAE, experimental autoimmune encephalomyelitis; LEW, Lewis; LEWHg, HgCl₂-injected LEW rats.

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