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(-CELL LINES() T)

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 th at expand in LEW rats produce IL-2 and prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune disease. The aim of thi s work was to investigate, using T cell lines derived from HgCl2-injec ted 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-gam ma and TGF-beta, and the protective effect is TGF-beta dependent since protection is abrogated by anti-TGF-beta treatment. These results ide ntify regulatory, TGF-beta-producing, autoreactive T cells that are di stinct from classical Th1 or Th2 and inhibit both Th1- and Th2-mediate d autoimmune diseases.