Williams R O, Whyte A
Department of Immunology, Babraham Institute, Cambridge, United Kingdom.
Cell Immunol. 1996 Jun 15;170(2):291-5. doi: 10.1006/cimm.1996.0163.
We have examined the ability of a mixture of two anti-CD4 mAbs to protect against collagen-induced arthritis. Anti-CD4 mAbs, administered around the time of primary immunisation with type II collagen in adjuvant, reduced the subsequent incidence of arthritis from 67 to 16% (P < 0.01 by Fisher exact test). However, anti-CD4 treatment 3 weeks after the primary immunisation did not significantly affect the incidence of arthritis. This result extends earlier findings concerning the lack of efficacy of anti-CD4 treatment in established collagen-induced arthritis. Next, the ability of anti-CD4 treatment to induce tolerance to bovine type II collagen (and hence protect against arthritis) was evaluated using a regime known to be capable of inducing tolerance to human gamma-globulin. Anti-CD4 treatment completely failed to induce tolerance to type II collagen, as judged by levels of anti-collagen antibody, or protect against collagen-induced arthritis. These findings highlight the potential limitations of anti-CD4 mAb depleting treatment in immunotherapy.
我们研究了两种抗CD4单克隆抗体的混合物预防胶原诱导性关节炎的能力。在佐剂中用II型胶原进行初次免疫时给予抗CD4单克隆抗体，可使随后的关节炎发病率从67%降至16%（Fisher精确检验，P<0.01）。然而，初次免疫3周后进行抗CD4治疗对关节炎发病率没有显著影响。这一结果扩展了先前关于抗CD4治疗在已建立的胶原诱导性关节炎中缺乏疗效的发现。接下来，使用已知能够诱导对人γ球蛋白耐受的方案，评估抗CD4治疗诱导对牛II型胶原耐受（从而预防关节炎）的能力。根据抗胶原抗体水平判断，抗CD4治疗完全未能诱导对II型胶原的耐受，也未能预防胶原诱导性关节炎。这些发现突出了抗CD4单克隆抗体消耗性治疗在免疫治疗中的潜在局限性。
