Ochi Hirofumi, Abraham Michal, Ishikawa Hiroki, Frenkel Dan, Yang Kaiyong, Basso Alexandre, 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, MA 02115, USA.
J Neurol Sci. 2008 Nov 15;274(1-2):9-12. doi: 10.1016/j.jns.2008.07.027. Epub 2008 Sep 18.
One of the major goals for the immunotherapy of autoimmune diseases is the induction of regulatory T cells that mediate immunologic tolerance. Parenteral administration of anti-CD3 monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. We have found that oral administration of anti-CD3 monoclonal antibody is biologically active in the gut and suppresses experimental autoimmune encephalomyelitis both prior to disease induction and at the height of disease. Oral anti-CD3 antibody acts by inducing a unique type of regulatory T cell characterized by latency-associated peptide (LAP) on its cell surface that functions in vivo and in vitro via TGF-beta dependent mechanism. Orally delivered antibody would not have side effects including cytokine release syndromes, thus oral anti-CD3 antibody is clinically applicable for chronic therapy. These findings identify a novel and powerful immunologic approach that is widely applicable for the treatment of human autoimmune conditions.
自身免疫性疾病免疫疗法的主要目标之一是诱导介导免疫耐受的调节性T细胞。静脉注射抗CD3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，口服抗CD3单克隆抗体在肠道中具有生物活性，并且在疾病诱导前和疾病高峰期均能抑制实验性自身免疫性脑脊髓炎。口服抗CD3抗体通过诱导一种独特类型的调节性T细胞发挥作用，该调节性T细胞的细胞表面具有潜伏期相关肽（LAP），通过转化生长因子-β（TGF-β）依赖性机制在体内和体外发挥作用。口服抗体不会产生包括细胞因子释放综合征在内的副作用，因此口服抗CD3抗体在临床上适用于慢性治疗。这些发现确定了一种新颖且强大的免疫方法，该方法广泛适用于治疗人类自身免疫性疾病。
