Duits A J, Aarden L A, Ernst L K, Capel P J, van de Winkel J G
Department of Immunology, University Hospital Utrecht, The Netherlands.
Clin Exp Immunol. 1993 May;92(2):225-31. doi: 10.1111/j.1365-2249.1993.tb03384.x.
Anti-CD3 MoAbs are widely used in T cell activation studies, and are effective in immunosuppressive therapy. We used a panel of mouse (m) anti-CD3 switch variant MoAbs of five different isotypes to study IL-6 release from accessory cells. Incubation of human (h) mononuclear cells with anti-CD3 MoAbs resulted in increased IL-6 levels with MoAbs of mIgG1 and mIgG2a isotypes, with no effect of mIgG2b or mIgA. This suggested involvement of IgG Fc receptors (Fc gamma R) in triggering IL-6 production. To evaluate the role of different Fc gamma R molecules individually we used a panel of hFc gamma R-transfected mouse fibroblasts, and Jurkat T cells as a model. IL-6 secretion by CD32 transfectants expressing the hFc gamma RIIa high-responder (HR) allelic form was triggered by mIgG1 anti-CD3 MoAb, with no effect of four other isotypes. None of the anti-CD3 MoAbs induced IL-6 secretion by CD32 transfectants expressing either a variant of this receptor, containing only a single intracellular amino acid (CT-), the hFc gamma RIIa low-responder (LR) allelic form, or hFc gamma RIIb1. hFc gamma RI (CD64) transfectants exhibited IL-6 production after incubation with mIgG2a anti-CD3 MoAb, and to a lesser extent with mIgG2b, and mIgG1 MoAb. Indirect involvement of T cells in triggering IL-6 secretion could be excluded by experiments in which transfectants were cultured with immobilized anti-CD3 MoAb. These data indicate that cross-linking of either hFc gamma RI, or hFc gamma RIIaHR by appropriate anti-CD3 MoAbs triggers IL-6 production of accessory cells, and not T cells. This may also take place in vivo during immunosuppressive therapy with anti-CD3 MoAbs, and related antibody-mediated immune responses.
抗CD3单克隆抗体广泛应用于T细胞活化研究，在免疫抑制治疗中也很有效。我们使用了一组具有五种不同亚型的小鼠抗CD3转换变体单克隆抗体来研究辅助细胞释放白细胞介素-6（IL-6）的情况。用人单核细胞与抗CD3单克隆抗体孵育后，mIgG1和mIgG2a亚型的单克隆抗体导致IL-6水平升高，而mIgG2b或mIgA则无此作用。这表明IgG Fc受体（FcγR）参与了IL-6产生的触发过程。为了分别评估不同FcγR分子的作用，我们使用了一组转染了人FcγR的小鼠成纤维细胞，并以Jurkat T细胞作为模型。表达hFcγRIIa高反应性（HR）等位基因形式的CD32转染细胞的IL-6分泌由mIgG1抗CD3单克隆抗体触发，其他四种亚型则无此作用。表达该受体变体（仅含单个细胞内氨基酸，CT-）、hFcγRIIa低反应性（LR）等位基因形式或hFcγRIIb1的CD32转染细胞，均未被任何抗CD3单克隆抗体诱导分泌IL-6。hFcγRI（CD64）转染细胞在与mIgG2a抗CD3单克隆抗体孵育后可产生IL-6，与mIgG2b和mIgG1单克隆抗体孵育时产生的IL-6较少。通过将转染细胞与固定化抗CD3单克隆抗体一起培养的实验，可以排除T细胞间接参与触发IL-6分泌的可能性。这些数据表明，合适的抗CD3单克隆抗体使hFcγRI或hFcγRIIaHR交联，可触发辅助细胞而非T细胞产生IL-6。这在使用抗CD3单克隆抗体进行免疫抑制治疗及相关抗体介导的免疫反应过程中，也可能在体内发生。
