Chatenoud Lucienne
Centre de l'Association Claude Bernard sur les Maladies Autoimmunes and Hôpital Necker Enfants Malades IRNEM, 161 Rue de Sèvres, 75015 Paris, France.
Nat Rev Immunol. 2003 Feb;3(2):123-32. doi: 10.1038/nri1000.
Although they were used initially as non-specific immunosuppressants in transplantation, CD3-specific monoclonal antibodies have elicited renewed interest owing to their capacity to induce immune tolerance. In mouse models of autoimmune diabetes, CD3-specific antibodies induce stable disease remission by restoring tolerance to pancreatic beta-cells. This phenomenon was extended recently to the clinic--preservation of beta-cell function in recently diagnosed patients with diabetes was achieved by short-term administration of a CD3-specific antibody. CD3-specific antibodies arrest ongoing disease by rapidly clearing pathogenic T cells from the target. Subsequently, they promote long-term T-cell-mediated active tolerance. Recent data indicate that transforming growth factor-beta-dependent CD4+CD25+ regulatory T cells might have a central role in this effect.
尽管CD3特异性单克隆抗体最初在移植中被用作非特异性免疫抑制剂，但由于它们具有诱导免疫耐受的能力，已引起了新的关注。在自身免疫性糖尿病的小鼠模型中，CD3特异性抗体通过恢复对胰腺β细胞的耐受性来诱导稳定的疾病缓解。这种现象最近已扩展到临床——通过短期给予CD3特异性抗体，在新诊断的糖尿病患者中实现了β细胞功能的保留。CD3特异性抗体通过迅速从靶标中清除致病性T细胞来阻止疾病进展。随后，它们促进长期的T细胞介导的主动耐受。最近的数据表明，转化生长因子-β依赖性CD4+CD25+调节性T细胞可能在这一效应中起核心作用。
