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 - PubMed (original) (raw)

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

F Bridoux et al. J Exp Med. 1997.

Abstract

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-gamma and TGF-beta, and the protective effect is TGF-beta dependent since protection is abrogated by anti-TGF-beta treatment. These results identify regulatory, TGF-beta-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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Figures

Figure 1

Figure 1

Ability of the LEWHg T cell lines to protect F1 rats against HgCl2-induced immune disorders. Antilaminin antibody titer (A and B) and serum IgE concentration (C and D) in HgCl2-injected rats (□, n = 25); normal rats ( , n = 5); rats injected with HgCl2 and, 2 wk before, with the LEWOVA (♦, n = 5), LEWHgA (▪, n = 21), LEWHgB (○, n = 3), LEWHgC (•, n = 3), LEWHgD (◫̶ , n = 3) or LEWHgE (⋄, n = 6) T cell line. AU, arbitrary units.

Figure 2

Figure 2

Incidence of F1 rats with glomerular IgG deposits (number in brackets) and immunofluorescence score in HgCl2-injected rats, control rats, and rats injected with HgCl2 and, 2 wk before, with one of the T cell lines. The immunofluorescence score concerns only rats that exhibited glomerular IgG deposits.

Figure 3

Figure 3

Effect of thymectomy and CD8+ cell depletion on the protective effect of the LEWHgA T cell line on HgCl2-induced disease. Antilaminin antibody titer (A) and serum IgE concentration (B) in HgCl2injected rats (□, n = 5), HgCl2-injected rats that received the LEWHgA T cell line two weeks before (▪, n = 9), thymectomized rats injected with HgCl2 and anti-CD8 mAb (◫̶ , n = 4), and thymectomized rats injected with the LEWHgA T cell line 2 wk before HgCl2 and anti-CD8 mAb administration (♦, n = 4).

Figure 4

Figure 4

Ability of the anti-TGF-β (1D11.16) mAb to reverse LEWHgAmediated protection from mercury disease. Antilaminin antibody titer (A) and serum IgE concentration (B) in HgCl2-injected rats (□, n = 5), and HgCl2-injected rats 2 wk after adoptive transfer of the LEWHgA T cell line treated (▴, n = 4) or not (▪, n = 4) with the 1D11.16 anti-TGF-β mAb (2 mg at day −2, 0, 3, 6, and 9 with respect to the first HgCl2 injection). The result is a pool of two independent experiments.

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