Flamand V, Donckier V, Abramowicz D, Goldman M, Vandenabeele P, Urbain J, Moser M, Leo O
Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Belgium.
Cell Immunol. 1994 Aug;157(1):239-48. doi: 10.1006/cimm.1994.1219.
The use of anti-CD3 monoclonal antibodies (mAb) to treat allograft rejection has been complicated by the morbidity observed during the first days of treatment, secondary to T cell activation and cytokine release. Available evidence in a mouse model indicates that F(ab')2 fragments of an anti-CD3 mAb are not mitogenic in vitro and can be injected in vivo without apparent toxicity. However, their immunosuppressive capacity is dramatically reduced, suggesting that long-term immunosuppression mediated by anti-CD3 antibodies in vivo may be associated to their mitogenic capacity. This paper demonstrates that a poorly mitogenic anti-CD3 mAb is able to induce potent immunosuppression in vivo with reduced morbidity. This finding suggests that immunosuppression in vivo by anti-CD3 mAbs is not directly related to their activation properties but nevertheless requires signaling capacities. Therefore, immunosuppression in vivo may be best achieved by using antibodies able to deliver an incomplete activation signal to T cells (thus avoiding systemic cytokine release), possibly leading to anergy. The implications of this study for the development of immunosuppressive antibodies are discussed.
使用抗CD3单克隆抗体（mAb）治疗同种异体移植排斥反应时，由于在治疗的最初几天观察到的发病率，这一过程变得复杂，该发病率继发于T细胞活化和细胞因子释放。小鼠模型中的现有证据表明，抗CD3 mAb的F(ab')2片段在体外无促有丝分裂作用，并且可以在体内注射而无明显毒性。然而，它们的免疫抑制能力显著降低，这表明抗CD3抗体在体内介导的长期免疫抑制可能与其促有丝分裂能力有关。本文证明，一种促有丝分裂能力较弱的抗CD3 mAb能够在体内诱导强效免疫抑制，且发病率降低。这一发现表明，抗CD3 mAb在体内的免疫抑制作用与其激活特性无直接关系，但仍需要信号传导能力。因此，通过使用能够向T细胞传递不完全激活信号（从而避免全身性细胞因子释放）的抗体，可能导致无反应性，从而最好地实现体内免疫抑制。本文讨论了这项研究对免疫抑制抗体开发的意义。
