Multiple mechanisms of B cell immunoregulation in man after administration of in vivo corticosteroids.
Multiple mechanisms of B cell immunoregulation in man after administration of in vivo corticosteroids.
复制标题
体内皮质类固醇给药后人体 B 细胞免疫调节的多种机制。
作者：
T. Cupps;L. C. Edgar;C. Thomas;A. Fauci
尽管皮质类固醇（CS）在治疗免疫介导的疾病中的广泛临床应用，但关于CS对B细胞功能的影响（如通过体外测定所测量的）相对知之甚少。本文报道了单剂量与数天的体内CS治疗对人外周血B细胞自发和丝裂原诱导的IG产生的影响。通过体外空斑形成细胞（PFC）试验测定，体内CS可增强单个B细胞自发产生IG。在体外将B细胞短暂暴露于CS时也观察到相同的反应增加，这表明仅短暂暴露于活性CS类似物即可产生增强的反应。体内CS对丝裂原诱导的IG产生的免疫调节作用更为复杂。美洲商陆有丝分裂原诱导的PFC反应被抑制4至5小时后，一个单一的体内药理剂量的CS，完全恢复24小时。相反，经过5天的CS课程，抑制PFC反应没有恢复，直到60小时后，最后一次给药。此外，几种抑制机制也在发挥作用。完成CS的5天疗程后10小时，外周血淋巴细胞中携带OKT 8抑制/细胞毒性T细胞表型的淋巴细胞相对富集，这与PFC反应降低一致。末次给药后36小时，T淋巴细胞特征恢复正常，而B细胞功能仍受到抑制。由于细胞亚群的重新分布以及细胞功能的改变，免疫应答的复杂、多方面的调节随体内CS给药的时间-剂量参数而变化。这些观察结果应提供额外的见解的异质性CS诱导的治疗效果。
Despite the extensive clinical use of corticosteroids (CS) in the treatment of immune-mediated diseases, relatively little is known concerning the effects of CS on B cell function as measured by in vitro assays. The effects of single-dose vs several days of in vivo CS therapy on the spontaneous and mitogen-induced Ig production by human peripheral blood B cells are reported here. Spontaneous Ig production by individual B cells was enhanced by in vivo CS as measured by an in vitro plaque-forming cell (PFC) assay. The same increased response was also observed with a brief in vitro exposure of the B cells to CS, which suggests that a mere brief exposure to an active CS analogue is all that is required to produce the enhanced response. The immunoregulatory effects of in vivo CS on mitogen-induced Ig production are more complex. Pokeweed mitogen-induced PFC responses were suppressed 4 to 5 hr after a single in vivo pharmacologic dose of CS, with complete recovery by 24 hr. In contrast, after a 5-day course of CS, the suppressed PFC response did not recover until 60 hr after the last dose. Moreover, several mechanisms of suppression were operative. Ten hours after completing the 5-day course of CS, there was a relative enrichment in the peripheral blood compartment of lymphocytes bearing the OKT8 suppressor/cytotoxic T cell phenotype that coincided with a depressed PFC response. At 36 hr after the last dose, the T lymphocyte profile returned to normal while B cell function remained suppressed. The complex, multifaceted modulation of the immune response, resulting from redistribution of cell subsets as well as altered cell functions, vary with time-dose parameters of in vivo CS administration. These observations should provide additional insights into the heterogeneity of CS-induced therapeutic effects.