J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/05/1769/07 $2.00
Volume 185, Number 10, May 19, 1997 1769-1775

Transforming Growth Factor  (TGF-)-dependent Inhibition of T Helper Cell 2 (Th2)-induced Autoimmunity by Self-Major Histocompatibility Complex (MHC) Class II-specific, Regulatory CD4⁺ T Cell Lines

By Frank Bridoux, Abdallah Badou, Abdelhadi Saoudi, Isabelle Bernard, Elvira Druet, Régine Pasquier, Philippe Druet, and Lucette Pelletier

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 × BN)F1 hybrids. The lines produce, in addition to IL-2, IFN- and TGF-, and the protective effect is TGF- dependent since protection is abrogated by anti-TGF- treatment. These results identify regulatory, TGF--producing, autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediated autoimmune diseases.

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