Vision Institute, Federal University of São Paulo, São Paulo, Brazil.
Scand J Immunol. 2010 Jul;72(1):31-7. doi: 10.1111/j.1365-3083.2010.02401.x.
The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-beta. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-beta and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-gamma secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-beta cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease.
促炎细胞因子在眼部自身免疫性疾病的发生和发展中起着关键作用。这些细胞因子的调节通常是通过免疫调节细胞因子如 IL-10 或 TGF-β来介导的。在这项研究中,我们研究了 Vogt-Koyanagi-Harada(VKH)患者的免疫调节细胞因子谱和天然调节性 T 细胞(nTreg)的频率。我们从 VKH 患者和健康对照者获得外周血单核细胞(PBMC)。通过 ELISA 测量 PBMC 在有或没有植物血球凝集素(PHA)培养后的上清液中的细胞因子谱,通过流式细胞术分析 CD4(+) Foxp3(+)和 CD25(high)Foxp3(+) T 调节细胞的百分比,通过实时定量 PCR 分析 Foxp3 表达的转录水平。在 VKH 患者疾病的非活动期,免疫调节细胞因子 TGF-β和 IL-10 增加。与健康对照组相比,我们观察到 VKH 患者的 CD4(+) Foxp3(+)和 CD25(high)Foxp3(+) T 细胞没有显著差异,FOXP3 mRNA 表达也没有减少。与健康对照组和疾病非活动期患者相比,我们在 VKH 患者疾病活动期的 PBMC 中观察到 IFN-γ分泌增加。我们的数据表明,IL-10 和 TGF-β细胞因子与疾病的缓解期有关,而不是 nTreg,可能在控制这种疾病方面发挥更相关的作用。