Bartholomew M, Brett S, Barber K, Rossman C, Crowe S, Tite J
Biology Division, Wellcome Research Laboratories, Beckenham, Kent, UK.
Immunology. 1995 May;85(1):41-8.
A fully humanized anti-CD4 antibody was studied for its effects on resting and activated CD4 T cells. Whereas the antibody was poorly lytic, it induced dramatic down-modulation of CD4 expression on both types of cell. In order to down-modulate CD4 on resting, normal CD4 T cells there was an absolute requirement for FcR-mediated cross-linking of the anti-CD4 antibody, and only CD4 levels were affected. When activated cloned T-cell lines were studied there was no requirement for cross-linking and several other cell surface markers were also affected. Although the total cellular CD4 was reduced in the down-modulated cells, as judged by Western blot analysis, that CD4 which remained was associated with p56lck. The results are discussed in relation to the potential use of humanized anti-CD4 antibodies in the therapy of autoimmune disease and the choice of antibody isotype for such a therapeutic antibody.
研究了一种完全人源化抗CD4抗体对静息和活化CD4 T细胞的作用。尽管该抗体的细胞裂解能力较弱，但它能显著下调这两种细胞上CD4的表达。为了下调静息、正常CD4 T细胞上的CD4，抗CD4抗体的FcR介导的交联是绝对必需的，且仅CD4水平受到影响。当研究活化的克隆T细胞系时，交联并非必需，其他几种细胞表面标志物也受到影响。通过蛋白质印迹分析判断，下调的细胞中总的细胞CD4减少，但剩余的CD4与p56lck相关。结合人源化抗CD4抗体在自身免疫性疾病治疗中的潜在用途以及此类治疗性抗体的抗体亚型选择对结果进行了讨论。
