Ochi Hirofumi, Abraham Michal, Ishikawa Hiroki, Frenkel Dan, Yang Kaiyong, Basso Alexandre S, Wu Henry, Chen Mei-Ling, Gandhi Roopali, Miller Ariel, Maron Ruth, Weiner Howard L
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Nat Med. 2006 Jun;12(6):627-35. doi: 10.1038/nm1408. Epub 2006 May 21.
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-beta-dependent mechanism. These findings identify a new immunologic approach that is widely applicable for the treatment of human autoimmune conditions.
自身免疫性疾病和移植免疫治疗的一个主要目标是诱导介导免疫耐受的调节性T细胞。黏膜免疫系统独具特色，因为接触抗原后优先诱导产生耐受，而调节性T细胞的诱导是口服耐受的主要机制。注射用CD3特异性单克隆抗体是一种已获批准用于人类移植的疗法，对自身免疫性糖尿病有效。我们发现，口服CD3特异性抗体在肠道具有生物活性，在疾病诱导前和疾病高峰期均能抑制自身免疫性脑脊髓炎。口服CD3特异性抗体可诱导CD4+ CD25- LAP+调节性T细胞，这些细胞表面含有潜伏相关肽（LAP），并通过转化生长因子-β依赖机制在体内外发挥作用。这些发现确定了一种广泛适用于治疗人类自身免疫性疾病的新免疫疗法。
