Patients treated with high‐dose intravenous immunoglobulin show selective activation of regulatory T cells
Patients treated with high‐dose intravenous immunoglobulin show selective activation of regulatory T cells
复制标题
使用高剂量静脉注射免疫球蛋白治疗的患者表现出调节性 T 细胞的选择性激活
DOI：
10.1111/cei.12102
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发表时间：
2013
影响因子：
4.6
通讯作者：
J. Kwekkeboom
中科院分区：
文献类型：
--
作者：
A. Tjon;T. Tha‐In;H. Metselaar;R. Gent;L. V. D. Laan;Zwier M. A. Groothuismink;P. T. Boekhorst;P. Hagen;J. Kwekkeboom
静脉注射免疫球蛋白（IVIg）用于治疗由体液和细胞免疫失调引起的自身免疫性和全身性炎症性疾病。在这项研究中，我们调查了静脉注射免疫球蛋白治疗是否可以调节调节性T细胞（T细胞）在人体内。在治疗前、治疗后即刻和治疗后7天，从接受低剂量（n = 12）或高剂量（n = 15）IVIg治疗的免疫缺陷或自身免疫性疾病IVIg治疗患者中采集血液。测量循环中CD 4 + CD 25+叉头盒蛋白3（FoxP 3+）T细胞和常规CD 4 + FoxP 3 − T辅助细胞（Tconv）的增殖和活化状态。在离体试验中测定了从指定时间点采集的血液中纯化的TdR的抑制能力。高剂量（而非低剂量）IVIg治疗增强了循环T细胞活化状态，如FoxP 3和人类白细胞抗原D相关（HLA-DR）表达增加所示，而循环T细胞数量保持不变。增强的激活持续至少7天后输注，并在IVIg治疗后第7天的抑制能力的纯化的TCLs从41%增加到70%。IVIg对Tconv的激活状态无影响。我们的结论是，高剂量IVIg治疗选择性激活TcR，并增强其在人体内的抑制功能。这种作用可能是IVIg恢复自身免疫性和全身性炎症性疾病患者失衡的免疫稳态的机制之一。
Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (Tregs) in humans in vivo. Blood was collected from IVIg‐treated patients with immunodeficiency or autoimmune disease who were treated with low‐dose (n = 12) or high‐dose (n = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4+CD25+forkhead box protein 3 (FoxP3+) Tregs and of conventional CD4+FoxP3− T‐helper cells (Tconv) were measured. The suppressive capacity of Tregs purified from blood collected at the time‐points indicated was determined in an ex‐vivo assay. High‐dose, but not low‐dose, IVIg treatment enhanced the activation status of circulating Tregs, as shown by increased FoxP3 and human leucocyte antigen D‐related (HLA‐DR) expression, while numbers of circulating Tregs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified Tregs was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of Tconv was not affected by IVIg. We conclude that high‐dose IVIg treatment activates Tregs selectively and enhances their suppressive function in humans in vivo. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.
影响因子：
20.3
作者：
Zeiser, Robert;Nguyen, Vu. H.;Negrin, Robert S.
通讯作者：
Negrin, Robert S.