Nature Medicine
- 12, 627 - 635 (2006)
Published online: 21 May 2006; | doi:10.1038/nm1408
Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+CD25-LAP+ T cellsHirofumi Ochi1, 3, Michal Abraham1, 3, Hiroki Ishikawa1, Dan Frenkel1, Kaiyong Yang1, Alexandre S Basso1, Henry Wu1, Mei-Ling Chen1, Roopali Gandhi1, Ariel Miller2, Ruth Maron1 & Howard L Weiner11
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. 2
Carmel Medical Center, Neuroimmunology Unit, Department of Neurology, 7 Michal Street, Haifa 34362, Israel. 3
These authors contributed equally to this work.
Correspondence should be addressed to Howard L Weiner hweiner@rics.bwh.harvard.edu 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- –dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.
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