T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome
T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome
复制标题
Wiskott-Aldrich 综合征患者的 T 细胞群体中，T 细胞受体多样性选择性地发生偏差。
DOI：
10.1016/j.jaci.2014.06.025
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发表时间：
2015-01-01
影响因子：
14.2
通讯作者：
Zhao, Xiaodong
中科院分区：
文献类型：
--
作者：
Wu, Junfeng;Liu, Dawei;Zhao, Xiaodong
背景：Wiskott-Aldrich综合征(Wiskott-Aldrich综合征)是一种以血小板减少、湿疹、免疫缺陷、自身免疫性疾病和淋巴系恶性肿瘤风险增加为特征的严重疾病。由于缺乏as蛋白表达而导致的免疫缺陷主要归因于T细胞功能缺陷。目前尚不清楚突变是否对不同T细胞亚群的T细胞受体(TCR)多样性产生不同的影响。目的：了解不同T细胞亚群TCR b链(Vb)可变区的偏斜程度和模式。方法：检测WAS患者外周血T细胞总数、分选的CD41和CD81T细胞的TCR谱系多样性。用互补决定区3分型方法分析比较了AS患者和年龄匹配的健康人外周血中CD45RA1(CD45RA1 CD45RO2细胞)和CD45RO 1(CD45RO2 CD45RO 1细胞)CD4 1和CD8 1 T细胞的TCRb转录本的互补决定区3。结果：强直性脊柱炎患者CD45RO 1、CD8 1 T细胞和CD8 1 TEMRA细胞的TCR谱多样性与年龄匹配的对照组相比明显偏斜。结论：基因突变选择性地影响CD45RO 1(记忆)CD 4 5 RO 1 T细胞的TCR谱的发育或扩增。
Background: Wiskott-Aldrich syndrome (WAS) is a severe disorder characterized by thrombocytopenia, eczema, immunodeficiency, and increased risk of autoimmune disease and lymphoid malignancies. The immunodeficiency caused by a lack of WAS protein expression has been mainly attributed to defective T-cell functions. Whether WAS mutations differentially influence the T-cell receptor (TCR) diversity of different T-cell subsets is unknown.Objective: We aimed to identify the degree and pattern of skewing in the variable region of the TCR b-chain (Vb) in different T-cell subsets from patients with WAS.Methods: The TCR repertoire diversity in total peripheral T cells, sorted CD4 1 and CD8 1 T cells, and CD45RA 1 (CD45RA 1 CD45RO 2 cells) and CD45RO 1 (CD45RA 2 CD45RO 1 cells) CD4 1 and CD8 1 T cells from patients with WAS and age-matched healthy control subjects was analyzed and compared by using spectratyping of complementarity-determining region 3. The complementaritydetermining region 3 of TCRb transcripts in CD45RA 1 CD4 1 and CD45RA 1 CD8 1 T cells, CD45RO 1 CD4 1 T cells, CD8 1 terminally differentiated effector memory T (Temra) cells, and naive CD8 1 T cells (CD8 1 CD45RO 2 CCR7 1 cells) from patients and control subjects were analyzed and compared by using high-throughput sequencing.Results: The TCR repertoire diversity in CD45RO 1 CD4 1 T cells and CD8 1 Temra cells of patients with WAS was significantly skewed in comparison with that seen in agematched control subjects.Conclusion: Our results indicate that WAS gene mutations selectively influence TCR repertoire development or expansion in CD45RO 1 (memory) CD4 1 T cells.