Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25-LAP+ T cells
Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25-LAP+ T cells
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DOI：
10.1038/nm1408
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发表时间：
2006-06-01
期刊：
影响因子：
82.9
通讯作者：
Weiner, Howard L.
中科院分区：
文献类型：
--
作者：
Ochi, Hirofumi;Abraham, Michal;Weiner, Howard L.
自身免疫性疾病和移植免疫治疗的一个主要目标是诱导调节免疫耐受的调节性T细胞。粘膜免疫系统是独特的，因为免疫耐受是在暴露于抗原后优先诱导的，而调节性T细胞的诱导是口服耐受的主要机制。肠外注射CD3特异性单抗是一种被批准用于人类移植的治疗方法，对自身免疫性糖尿病有效。我们发现，口服CD3特异性抗体在肠道中具有生物活性，在疾病诱导之前和疾病高峰期都能抑制自身免疫性脑脊髓炎。口服CD3特异性抗体可诱导表面含有潜伏期相关肽(LAP)的CD4(+)CD25(-)LAP(+)调节性T细胞，并通过一种依赖于转化生长因子的机制在体外和体内发挥作用。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的免疫学方法。
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.