Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390-9072, USA.
Clin Immunol. 2013 May;147(2):105-19. doi: 10.1016/j.clim.2013.02.015. Epub 2013 Mar 6.
Daily administration of FDA-approved glatiramer acetate (GA) has beneficial effects on clinical course of relapsing remitting multiple sclerosis (RRMS). Although mechanisms of GA-action have been widely investigated and partially understood, immediate immune dynamics following GA-therapy are unknown. In the present study, we characterized the immediate effects of GA on phenotype, quantity and function of immune cells in MS patients. Prominent changes in immune cells were detected within 4-12h post-first GA-injection. T-cell modulation included significantly decreased CD4/CD8 ratio, perturbed homeostasis of predominantly CD8+ T-cells, significant enhancement in CD8+ T-cell mediated suppression and inhibitory potential of induced CD4-suppressors. Changes in APC were restricted to monocytes and included reduced stimulatory capacity in MLR and significantly increased IL-10 and TNF-α production. Our study provides the first evidence that GA treatment induces rapid immunologic changes within hours of first dose. Interestingly, these responses are not only restricted to innate immune cells but also include complex modulation of T-cell functionality.
每日给予美国食品和药物管理局批准的醋酸格拉替雷(GA)对复发缓解型多发性硬化症(RRMS)的临床病程有有益的影响。尽管 GA 作用机制已被广泛研究并部分了解,但 GA 治疗后的即时免疫动态尚不清楚。在本研究中,我们描述了 GA 对 MS 患者免疫细胞表型、数量和功能的即时影响。在首次 GA 注射后 4-12 小时内检测到免疫细胞的显著变化。T 细胞调节包括 CD4/CD8 比值显著降低、主要 CD8+T 细胞的稳态失调、CD8+T 细胞介导的抑制作用显著增强以及诱导的 CD4 抑制物的抑制潜能。APC 的变化仅限于单核细胞,包括在 MLR 中的刺激能力降低,以及 IL-10 和 TNF-α产生的显著增加。我们的研究首次提供了证据,表明 GA 治疗在首次剂量后数小时内诱导快速免疫变化。有趣的是,这些反应不仅限于先天免疫细胞,还包括 T 细胞功能的复杂调节。