Renz H, Brodie C, Bradley K, Leung D Y, Gelfand E W
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Allergy Clin Immunol. 1994 Mar;93(3):658-68. doi: 10.1016/s0091-6749(94)70078-8.
It has been recently recognized that the obligate requirement for T cells in the development of IgE responses can be substituted for by anti-CD40 antibody. In this study of patients with atopic dermatitis and high IgE levels, we have analyzed the role of the CD40 molecule in IgE production. Costimulation of peripheral blood mononuclear cells (PBMCs) from normal donors with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody resulted in a selective increase in IgE production; either reagent alone, however, was ineffective. In contrast, addition of anti-CD40 monoclonal antibody alone to PBMCs or B cells from patients with atopic dermatitis markedly increased IgE production, even in the absence of exogenous IL-4. With the use of an ELISA spot assay, this increase in IgE production was attributed to an expansion of IgE-secreting B cells. In anti-IgM-stimulated lymphocyte cultures from patients with atopic dermatitis the costimulation with anti-CD40 induced strong lymphocyte proliferation. Similar results were observed with anti-IgM plus IL-4. The augmentation induced by anti-CD40 was inhibited by addition of anti-IL4 to anti-CD40-treated atopic dermatitis cells. In normal subjects the effects of anti-CD40 alone on IgE production could be observed after pretreatment of normal PBMCs with IL-4 for 3 days. The effects of anti-CD40 in atopic dermatitis may be explained in part by differences in CD40 expression. In freshly isolated PBMCs from patients with atopic dermatitis, the mean fluorescence intensity of CD40 expression on B cells was increased when compared with PBMCs from nonatopic donors, ans stimulation of normal or atopic dermatitis PBMCs with IL-4 increased the intensity of CD40 staining of cells.
最近人们认识到，在IgE反应的发生过程中对T细胞的绝对需求可以被抗CD40抗体所替代。在这项针对特应性皮炎和高IgE水平患者的研究中，我们分析了CD40分子在IgE产生中的作用。用白细胞介素-4（IL-4）和抗CD40单克隆抗体共同刺激正常供体的外周血单个核细胞（PBMC）会导致IgE产生选择性增加；然而，单独使用任何一种试剂都无效。相比之下，单独向特应性皮炎患者的PBMC或B细胞中添加抗CD40单克隆抗体，即使在没有外源性IL-4的情况下，也会显著增加IgE的产生。通过酶联免疫斑点分析，IgE产生的这种增加归因于分泌IgE的B细胞的扩增。在来自特应性皮炎患者的抗IgM刺激的淋巴细胞培养物中，抗CD40的共同刺激诱导了强烈的淋巴细胞增殖。抗IgM加IL-4也观察到了类似的结果。向抗CD40处理的特应性皮炎细胞中添加抗IL-4可抑制抗CD40诱导的增强作用。在正常受试者中，在用IL-4预处理正常PBMC 3天后，可以观察到单独使用抗CD40对IgE产生的影响。抗CD40在特应性皮炎中的作用部分可能是由CD40表达的差异所解释的。与非特应性供体的PBMC相比，在新鲜分离的特应性皮炎患者的PBMC中，B细胞上CD40表达的平均荧光强度增加，并且用IL-4刺激正常或特应性皮炎PBMC会增加细胞CD40染色的强度。
