Department of Immunology, National Institute of Neuroscience (K.K., M.N., W.S., Y.L., T.Y.), and Multiple Sclerosis Center (W.S., T.O., M.A., Y.L., T.Y.) and Department of Neurology (Y.L., M.M.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; and Department of Neurology (K.K., R.T.), Kyoto University Graduate School of Medicine, Japan.
Neurol Neuroimmunol Neuroinflamm. 2016 Mar 3;3(2):e210. doi: 10.1212/NXI.0000000000000210. eCollection 2016 Apr.
To compare effects of natalizumab on inflammatory and regulatory T cells with regard to expression of α4-integrin (CD49d).
Twenty-seven natalizumab-naive and 8 natalizumab-treated patients with multiple sclerosis (MS), 7 patients with neuromyelitis optica (NMO) or NMO spectrum disorder, and 8 healthy controls were included. The positive rate of CD49d was analyzed and compared among T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells (CD49d+Th1, CD49d+Th17, and CD49d+Treg, respectively).
Natalizumab treatment increased CD49d ratios, CD49d+Th1/CD49d+Treg, and CD49d+Th17/CD49d+Treg. This indicates larger reduction of the CD49d+ population in Treg cells than in Th1 or Th17 cells. The CD49d ratios of 2 patients who experienced exacerbation during natalizumab treatment were remarkably higher than those of the other natalizumab-treated patients. Natalizumab treatment increased the expression of TBX21, RORC, interferon (IFN)-γ, and interleukin (IL)-17A, and decreased the expression of FOXP3 in CD49d+ memory CD4 T cells. Natalizumab treatment also increased the amount of IFN-γ and IL-17A secreted by CD49d+ memory CD4 T cells.
The reduction rate of the CD49d+ population in Treg cells was larger than that in Th1 or Th17 cells. Although the large reduction in CD49d+ population is beneficial for MS, the proinflammatory state of residual CD49d+ cells might, in part, explain the presence of disease activity under natalizumab treatment.
比较那他珠单抗对α4-整合素（CD49d）表达的调节性 T 细胞和炎症性 T 细胞的影响。
纳入 27 例初治多发性硬化症（MS）患者、8 例那他珠单抗治疗患者、7 例视神经脊髓炎（NMO）或 NMO 谱系障碍患者和 8 例健康对照者。分析并比较了 T 辅助细胞 1（Th1）、T 辅助细胞 17（Th17）和调节性 T（Treg）细胞（CD49d+Th1、CD49d+Th17 和 CD49d+Treg）中 CD49d 的阳性率。
那他珠单抗治疗增加了 CD49d 比值、CD49d+Th1/CD49d+Treg 和 CD49d+Th17/CD49d+Treg。这表明 Treg 细胞中 CD49d+群体的减少幅度大于 Th1 或 Th17 细胞。在那他珠单抗治疗期间发生恶化的 2 例患者的 CD49d 比值明显高于其他那他珠单抗治疗患者。那他珠单抗治疗增加了 CD49d+记忆性 CD4 T 细胞中 TBX21、RORC、干扰素（IFN）-γ 和白细胞介素（IL）-17A 的表达，降低了 FOXP3 的表达。那他珠单抗治疗还增加了 CD49d+记忆性 CD4 T 细胞分泌的 IFN-γ 和 IL-17A。
Treg 细胞中 CD49d+群体的减少幅度大于 Th1 或 Th17 细胞。尽管 CD49d+群体的大量减少有利于 MS，但残留 CD49d+细胞的促炎状态可能部分解释了那他珠单抗治疗下疾病活动的存在。
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