Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Int Immunol. 2009 Dec;21(12):1329-40. doi: 10.1093/intimm/dxp100. Epub 2009 Oct 11.
MBP-specific autoreactive T cells are considered pro-inflammatory T cells and thought to play an important role in the pathogenesis of multiple sclerosis (MS). Here, we report that MBP(83-99)-specific T cells generated from MS patients (n = 7) were comprised of pro-inflammatory and regulatory subsets of distinct phenotypes. The pro-inflammatory phenotype was characterized by high production of IFN-gamma, IL-6, IL-21 and IL-17 and low expression of FOXP3, whereas the regulatory subset expressed high levels of FOXP3 and exhibited potent regulatory functions. The regulatory subset of MBP-specific T cells appeared to expand from the CD4(+)CD25(-) T-cell pool. Their FOXP3 expression was stable, independent of the activation state and it correlated with suppressive function and inversely with the production of IFN-gamma, IL-6, IL-21 and IL-17. In contrast, the phenotype and function of FOXP3(low) MBP-specific T cells were adaptive and dependent on IL-6. The higher frequency of FOXP3(high) MBP-specific T cells was observed when IL-6 was neutralized in the culture of PBMC with MBP. The study provides new evidence that MBP-specific T cells are susceptible to pro-inflammatory cytokine milieu and act as either pro-inflammatory or regulatory T cells.
髓鞘碱性蛋白（MBP）特异性自身反应性 T 细胞被认为是促炎 T 细胞，被认为在多发性硬化症（MS）的发病机制中发挥重要作用。在这里，我们报告称，从 MS 患者（n=7）中产生的 MBP（83-99）特异性 T 细胞由具有不同表型的促炎和调节亚群组成。促炎表型的特征是 IFN-γ、IL-6、IL-21 和 IL-17 的高产生和 FOXP3 的低表达，而调节亚群表达高水平的 FOXP3 并表现出有效的调节功能。MBP 特异性 T 细胞的调节亚群似乎从 CD4(+)CD25(-)T 细胞池中扩增而来。它们的 FOXP3 表达稳定，不依赖于激活状态，与抑制功能相关，与 IFN-γ、IL-6、IL-21 和 IL-17 的产生呈负相关。相比之下，FOXP3(low)MBP 特异性 T 细胞的表型和功能是适应性的，依赖于 IL-6。当用 MBP 对 PBMC 的培养物进行 IL-6 中和时，观察到 FOXP3(high)MBP 特异性 T 细胞的频率更高。该研究提供了新的证据表明，MBP 特异性 T 细胞易受促炎细胞因子环境的影响，并表现为促炎或调节性 T 细胞。
