Renz H, Mazer B D, Gelfand E W
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Immunol. 1990 Dec 1;145(11):3641-6.
The present study examines the role of the immunosuppressive agents methylprednisolone (MPN) and cyclosporin (Cs)A on IL-4-dependent IgE and IgG production. Addition of optimal amounts of IL-4 (100 U/ml) to cultures of tonsil mononuclear cells resulted in a mean increase in IgG production of 175% and in IgE production of 2460%. Frequency analysis of IgE- and IgG-producing B cells, using an ELISA spot assay, showed parallel increases in both Ig production and numbers of Ig-secreting B cells. IgE production was also enhanced by addition of IL-2 (10 U/ml) and maximal IgE production was obtained with a combination of IL-4 and IL-2. MPN (10(-7) M) and CsA (1 microgram/ml) markedly reduced IL4-induced IgE and IgG production as well as numbers of Ig-secreting cells in a dose-dependent fashion. The suppression of Ig production by the cyclosporins was restricted to the immunosuppressive compounds CsA, CsG, and dihydro-CsD, but not the nonimmunosuppressive drug CsH. Delayed addition of CsA revealed that inhibition was maximal when the drug was added during the first 48 h after addition of IL-4 to the culture. Addition of IL-2 (10 U/ml) partially overcame the inhibition induced by CsA. In coculture experiments, in which separated T or B cells were precultured with the drugs and the cells were then combined and further incubated in the presence of IL-4, the suppressive effects of CsA on IgE production were related to pretreatment of the T but not B cells. The maximum inhibiting effects of MPN were similarly observed when the drug was present in the cultures from the beginning, and addition of IL-2 also partially reversed this inhibition. In contrast to the results with CsA, pretreatment of the B but not T cells with MPN-reduced IgE production. These studies demonstrate that IL-4 increases both numbers of IgE-secreting cells as well as IgE production and CsA and MPN differentially affect the responding T and B cells, resulting in inhibition of Ig production.
本研究考察了免疫抑制剂甲泼尼龙（MPN）和环孢素（Cs）A对白细胞介素-4（IL-4）依赖的免疫球蛋白E（IgE）和免疫球蛋白G（IgG）产生的作用。向扁桃体单个核细胞培养物中添加最适量的IL-4（100 U/ml），导致IgG产生平均增加175%，IgE产生平均增加2460%。采用酶联免疫斑点分析对产生IgE和IgG的B细胞进行频率分析，结果显示Ig产生和分泌Ig的B细胞数量均呈平行增加。添加白细胞介素-2（IL-2，10 U/ml）也可增强IgE产生，且IL-4与IL-2联合使用时可获得最大的IgE产生量。MPN（10⁻⁷ M）和CsA（1微克/毫升）以剂量依赖方式显著降低IL-4诱导的IgE和IgG产生以及分泌Ig的细胞数量。环孢素对Ig产生的抑制作用仅限于免疫抑制化合物CsA、CsG和二氢CsD，而非免疫抑制药物CsH则无此作用。延迟添加CsA显示，在向培养物中添加IL-4后的最初48小时内添加该药物时，抑制作用最大。添加IL-2（10 U/ml）可部分克服CsA诱导的抑制作用。在共培养实验中，将分离的T细胞或B细胞与药物预培养，然后将细胞混合，并在IL-4存在下进一步孵育，CsA对IgE产生的抑制作用与T细胞而非B细胞的预处理有关。当从一开始就在培养物中加入MPN时，同样观察到其最大抑制作用，添加IL-2也可部分逆转这种抑制作用。与CsA的结果相反，用MPN预处理B细胞而非T细胞可降低IgE产生。这些研究表明，IL-4可增加分泌IgE的细胞数量以及IgE产生，且CsA和MPN对反应性T细胞和B细胞有不同影响，从而导致Ig产生受到抑制。
