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Prevention of autoimmune attack by targeting specific T‐cell receptors in a severe combined immunodeficiency mouse model of myasthenia gravis
Author(s) -
Aissaoui Abderrahim,
KlingelSchmitt Isabelle,
Couderc Jacques,
Chateau Danielle,
Romagne Francois,
Jambou Florence,
Vincent Angela,
Levasseur Philippe,
Eymard Bruno,
Maillot Marie Christine,
Galanaud Pierre,
BerrihAknin Sonia,
CohenKaminsky Sylvia
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199910)46:4<559::aid-ana3>3.0.co;2-s
Subject(s) - myasthenia gravis , immunology , autoantibody , acetylcholine receptor , immunodeficiency , biology , immune system , receptor , antibody , autoimmune disease , interleukin 2 , population , t cell , medicine , biochemistry , environmental health
Myasthenia gravis (MG) is an autoimmune disease targeting the skeletal muscle acetylcholine receptor. We have previously demonstrated a selection bias of CD4 + T cells expressing the Vβ5.1 T‐cell receptor gene in the thymus of HLA‐DR3 patients with MG. To evaluate the pathogenicity of these cells, severe combined immunodeficiency mice engrafted with MG thymic lymphocytes were treated with anti‐Vβ5.1 antibody. Signs of pathogenicity (eg, acetylcholine receptor loss and complement deposits at the muscle end plates of chimeric mice) were prevented in anti‐Vβ5.1–treated severe combined immunodeficiency chimeras. Pathogenicity was mediated by autoantibodies against acetylcholine receptor. Thymic cells depleted of Vβ5.1‐positive cells in vitro before cell transfer were nonpathogenic, indicating that Vβ5.1‐positive cells are involved in the production of pathogenic autoantibodies. Acetylcholine receptor loss was prevented by Vβ5.1 targeting in HLA‐DR3 patients only, demonstrating specificity for HLA‐DR3–peptide complexes. The action of the anti‐Vβ5.1 antibody involved both the in vivo depletion of Vβ5.1‐expressing cells and an increase in the interferon‐γ/interleukin‐4 ratio, pointing to an immune deviation–based mechanism. This demonstration that a selective and specific T‐helper cell population is involved in controlling pathogenic autoantibodies in MG holds promise for the treatment of MG.