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- Title
Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4<sup>+</sup>CD25<sup>−</sup>LAP<sup>+</sup> T cells.
- Authors
Ochi, Hirofumi; Abraham, Michal; Ishikawa, Hiroki; Frenkel, Dan; Yang, Kaiyong; Basso, Alexandre S.; Wu, Henry; Mei-Ling Chen; Gandhi, Roopali; Miller, Ariel; Maron, Ruth; Weiner, Howard L.
- 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.
- Subjects
CD antigens; AUTOIMMUNE diseases; ENCEPHALOMYELITIS; IMMUNE system; IMMUNOLOGY
- Publication
Nature Medicine, 2006, Vol 12, Issue 6, p627
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1408