Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy.
Mult Scler. 2012 Jun;18(6):788-98. doi: 10.1177/1352458511427720. Epub 2011 Nov 15.
Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.
T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.
Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory-like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.
The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.
干扰素-β用于降低多发性硬化症的疾病活动度，但它的作用尚未完全了解，患者之间的个体治疗反应存在差异，尚未确定预测临床获益的生物标志物。由于已知多发性硬化症患者存在调节性 T 细胞亚群的缺陷，我们研究了干扰素-β治疗是否会诱导对治疗有生物学反应的患者的两种主要调节性 T 细胞（Treg）类别（天然和 IL-10 分泌诱导的 Tr1 亚群）的改变。
通过流式细胞术确定 T 细胞表型，同时使用实时 PCR 通过 MxA 测定评估干扰素-β的生物活性，并测量外周血单个核细胞中 IL-10 和 CD46 分子的 RNA，这些细胞用抗 CD46 和抗 CD3 单克隆抗体刺激，已知可扩增类似 Tr1 的群体。
干扰素-β诱导天然 Treg 亚群重新分布，幼稚 Treg 向表达体内抑制活性所需的 CCR7 分子的“中央记忆样”Treg 群体转移。此外，在一组接受治疗的患者中，CD46/CD3 共刺激可能通过调节类似 Tr1 的亚群增加了 IL-10 和 CD46 的 RNA 产生。该组在两年的治疗后显示出较低的中位 EDSS 评分。
“中央记忆样”亚群的选择性增加和类似 Tr1 群体的参与可能是干扰素-β发挥其有益作用的两种机制。IL-10 和 CD46 的 RNA 定量可用于识别对干扰素-β治疗反应不同的患者。
