Wofsy D, Seaman W E
J Exp Med. 1985 Feb 1;161(2):378-91. doi: 10.1084/jem.161.2.378.
Autoimmune NZB/NZW mice were treated with weekly injections of monoclonal antibody (mAb) to L3T4, an antigen expressed on a distinct subpopulation of T cells that respond to class II major histocompatibility antigens. Treatment with anti-L3T4 depleted circulating target cells, reduced autoantibody production, retarded renal disease, and prolonged life relative to control mice treated either with saline or with purified nonimmune rat IgG. These findings establish that autoimmune disease in NZB/NZW mice is regulated by T cells. In contrast to mice treated with nonimmune rat IgG, mice treated with rat anti-L3T4 mAb developed little or no antibody to rat Ig. Thus, the benefits of treatment with anti-L3T4 were achieved while minimizing the risks associated with a host immune response to therapy. This study raises the possibility that treatment with mAb against Leu-3/T4, the human homologue for L3T4 might be effective in the treatment of certain autoimmune diseases in people.
将针对L3T4的单克隆抗体(mAb)每周注射给自身免疫性NZB/NZW小鼠,L3T4是一种在对II类主要组织相容性抗原产生反应的T细胞特定亚群上表达的抗原。与用盐水或纯化的非免疫大鼠IgG处理的对照小鼠相比,用抗L3T4处理可耗尽循环中的靶细胞,减少自身抗体产生,延缓肾脏疾病,并延长寿命。这些发现证实NZB/NZW小鼠中的自身免疫性疾病受T细胞调节。与用非免疫大鼠IgG处理的小鼠相比,用大鼠抗L3T4 mAb处理的小鼠产生很少或不产生抗大鼠Ig的抗体。因此,在用抗L3T4治疗时,在将与宿主对治疗的免疫反应相关的风险降至最低的同时实现了治疗益处。这项研究提出了这样一种可能性,即针对L3T4的人类同源物Leu-3/T4的单克隆抗体治疗可能对治疗人类某些自身免疫性疾病有效。