Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25LAP+ T cells

H Ochi, M Abraham, H Ishikawa, D Frenkel, K Yang… - Nature medicine, 2006 - nature.com
H Ochi, M Abraham, H Ishikawa, D Frenkel, K Yang, AS Basso, H Wu, ML Chen, R Gandhi
Nature medicine, 2006nature.com
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 …
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+CD25LAP+ 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.
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