Author: ["Hirofumi Ochi","Michal Abraham","Hiroki Ishikawa","Dan Frenkel","Kaiyong Yang","Alexandre S Basso","Henry Wu","Mei-Ling Chen","Roopali Gandhi","Ariel Miller","Ruth Maron","Howard L Weiner"]
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Abstract
A major goal of immunotherapy for autoimmune diseases and transplantation is induction of regulatory T cells that mediate immunologic tolerance. The mucosal immune system is unique, as tolerance is preferentially induced after exposure to antigen, and induction of regulatory T cells is a primary mechanism of oral tolerance. Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We found that orally administered CD3-specific antibody is biologically active in the gut and suppresses autoimmune encephalomyelitis both before induction of disease and at the height of disease. Orally administered CD3-specific antibody induces CD4+CD25−LAP+ regulatory T cells that contain latency-associated peptide (LAP) on their surface and that function in vitro and in vivo through a TGF-β–dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.Cite this article
Ochi, H., Abraham, M., Ishikawa, H. et al. Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25−LAP+ T cells. Nat Med 12, 627–635 (2006). https://doi.org/10.1038/nm1408 