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LAG‐3 (Lymphocyte Activation Gene‐3) Negatively Regulates Environmentally‐Induced Autoimmune Disease
Author(s) -
Jha Vibha,
Workman Creg J.,
Vignali Dario,
Monestier Marc
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.669.3
Subject(s) - autoimmunity , immunology , autoantibody , foxp3 , autoimmune disease , biology , chemistry , antibody , immune system
After exposure to subtoxic levels of mercury (Hg), genetically susceptible mouse strains develop an autoimmune disease characterized by the production of highly specific IgG anti‐nucleolar autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized to the disease by a single low dose administration of Hg. Previous studies from our lab demonstrated that CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) control the induction and maintenance of tolerance to Hg. Lymphocyte Activation Gene‐3 (LAG‐3) is a CD4‐related, MHC‐class II binding molecule expressed on activated T cells and NK cells. LAG‐3 is an inhibitory molecule that maintains lymphocyte homeostatic balance by controlling effector T cell expansion and contributing to the suppressive functions of Tregs. In our model, administration of anti‐LAG‐3 monoclonal antibody broke tolerance to Hg resulting in autoantibody production and an increase in the levels of serum IgE. In addition, LAG‐3‐deficient B6.H2 s mice had increased susceptibility to Hg‐induced autoimmunity, as illustrated by an increase in autoantibody levels and polyclonal activation when compared to the wild‐type controls. Therefore, LAG‐3 exerts an important regulatory effect on autoimmunity elicited by a common environmental pollutant.