Department of Pediatrics, School of Medicine, University of California San Diego and Rady Children's Hospital, La Jolla, CA, USA.
Clin Exp Immunol. 2013 Dec;174(3):337-44. doi: 10.1111/cei.12182.
The expansion of regulatory T cells (Treg ) controls inflammation in children with acute Kawasaki disease (KD). Blockade of tumour necrosis factor (TNF)-α is an emerging therapy for KD patients with refractory inflammation, but there is concern that this therapy could impede the host immune regulation. To define the effect of TNF-α blockade, we conducted ex-vivo immune-monitoring in KD subjects who participated in a randomized, double-blind, placebo-controlled clinical trial of the addition of infliximab to standard intravenous immunoglobulin (IVIG) therapy. We enumerated circulating myeloid and plasmocytoid dendritic cells (DC), regulatory T cells (Treg ) and memory T cells (Tmem ) in 14 consecutive, unselected KD patients (seven treated with IVIG, seven with IVIG + infliximab) at three time-points: (i) acute phase prior to treatment, (ii) subacute phase and (iii) convalescent phase. Myeloid DC (mDC), but not plasmacytoid DC (pDC), were numerous in the peripheral blood in acute KD subjects and decreased in the subacute phase in both IVIG(-) and IVIG (+) infliximab-treated groups. The co-stimulatory molecule for antigen presentation to T cells and CD86 decreased in mDC from acute to subacute time-points in both treatment groups, but not in the single patient who developed coronary artery aneurysms. We also defined tolerogenic mDC that expand in the subacute phase of KD not impaired by infliximab treatment. Treg and Tmem expanded after treatment with no significant differences between the two groups. Treatment of KD patients with infliximab does not adversely affect generation of tolerogenic mDC or the development of T cell regulation and memory.
调节性 T 细胞（Treg）的扩增可控制川崎病（KD）患儿的炎症。肿瘤坏死因子（TNF）-α的阻断是一种新兴的治疗方法，适用于难治性炎症的 KD 患者，但人们担心这种治疗方法可能会阻碍宿主的免疫调节。为了确定 TNF-α阻断的效果，我们对参与英夫利昔单抗联合静脉注射免疫球蛋白（IVIG）标准治疗的 KD 患者进行了随机、双盲、安慰剂对照的临床试验，对其进行了体外免疫监测。我们在 14 名连续、未经选择的 KD 患者（7 名接受 IVIG 治疗，7 名接受 IVIG+英夫利昔单抗治疗）的三个时间点（i）治疗前急性期、（ii）亚急性期和（iii）恢复期，计数了循环髓样和浆细胞样树突状细胞（DC）、调节性 T 细胞（Treg）和记忆 T 细胞（Tmem）。急性 KD 患者外周血中髓样 DC（mDC）较多，浆细胞样 DC（pDC）较少，且在 IVIG（-）和 IVIG+英夫利昔单抗治疗组的亚急性期均减少。在两个治疗组中，从急性期到亚急性期，mDC 上的共刺激分子（用于向 T 细胞呈递抗原）和 CD86 减少，但在单个发生冠状动脉瘤的患者中没有减少。我们还定义了耐受 mDC，其在 KD 的亚急性期扩增不受英夫利昔单抗治疗的影响。Treg 和 Tmem 在治疗后扩增，两组之间无显著差异。KD 患者用英夫利昔单抗治疗不会对耐受 mDC 的产生或 T 细胞调节和记忆的发育产生不利影响。
