Plater-Zyberk C, Taylor P C, Blaylock M G, Maini R N
Kennedy Institute of Rheumatology, London, UK.
Clin Exp Immunol. 1994 Dec;98(3):442-7. doi: 10.1111/j.1365-2249.1994.tb05510.x.
Collagen-induced arthritis has been widely used as an animal model of rheumatoid arthritis. We have used this model with a view to determining potential therapeutic targets for the treatment of human disease. To do this we have attempted to modulate the progression of established arthritis over a 10-day time period following the first appearance of disease, by i.p. injection of one of three different MoAbs. These consist of a rat IgG2a specific for the CD5 antigen expressed on all T cells and a subpopulation of B cells, a mouse IgG2b recognizing the CD72 antigen, and a rat IgM specific for the B220 molecule, CD72 and B220 both being expressed on all B cells. None of the three MoAbs had depleting activity in vivo. The progression of arthritis was monitored both clinically, and histologically. The effects of treatment with anti-CD5 and anti-CD72 antibodies were compared with control antibodies of the same species class and subclass. In the case of anti-B220 antibodies, the effects of treatment were compared with administration of PBS. Of these MoAbs, only treatment with anti-CD5 resulted in disease amelioration with significant decrease in disease severity in 60% of the animals. These changes became apparent 6 days after initiation of treatment. There were no significant differences in serum levels of IgG antibodies to native bovine collagen type II between the groups of treated and control mice. Possible mechanisms underlying the modification of disease expression following treatment with anti-CD5 MoAb are discussed.
胶原诱导性关节炎已被广泛用作类风湿性关节炎的动物模型。我们使用该模型旨在确定治疗人类疾病的潜在治疗靶点。为此，我们试图在疾病首次出现后的10天时间内，通过腹腔注射三种不同的单克隆抗体（MoAb）之一来调节已建立的关节炎的进展。这三种单克隆抗体包括一种对所有T细胞和一部分B细胞上表达的CD5抗原具有特异性的大鼠IgG2a、一种识别CD72抗原的小鼠IgG2b以及一种对B220分子具有特异性的大鼠IgM，CD72和B220均在所有B细胞上表达。这三种单克隆抗体在体内均无清除活性。通过临床和组织学方法监测关节炎的进展。将抗CD5和抗CD72抗体的治疗效果与相同物种类别和亚类的对照抗体进行比较。对于抗B220抗体，将治疗效果与给予磷酸盐缓冲液（PBS）进行比较。在这些单克隆抗体中，只有抗CD5治疗导致疾病改善，60%的动物疾病严重程度显著降低。这些变化在治疗开始后6天变得明显。治疗组和对照组小鼠血清中针对天然牛II型胶原的IgG抗体水平没有显著差异。文中讨论了抗CD5单克隆抗体治疗后疾病表达改变的潜在机制。
