Clonal Expansion of β-T Lymphocytes With Inverted Jβ1 Bias in Familial Hemophagocytic Lymphohistiocytosis
Clonal Expansion of β-T Lymphocytes With Inverted Jβ1 Bias in Familial Hemophagocytic Lymphohistiocytosis
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家族性噬血细胞性淋巴组织细胞增多症中具有反向 Jβ1 偏向的 β-T 淋巴细胞克隆扩增
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
S. Mizutani
中科院分区：
文献类型：
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作者：
M. Nagano;N. Kimura;E. Ishii;N. Yoshida;Tetsuya Yoshida;M. Sako;S. Hibi;S. Imashuku;S. Miyazaki;T. Hara;S. Mizutani
家族性噬血细胞性淋巴组织细胞增生症是一种罕见但致命的婴儿疾病。关于FHL患者T细胞的克隆性，以前没有报道。我们在这里分析了5例FHL患者的T细胞受体可变区基因（TCR V）的逆转录聚合酶链反应（RT-PCR），β链的连接区基因（Jbeta）-PCR，单链构象多态性（SSCP）和序列分析的克隆性。分别在3/5和4/4例检查患者中观察到高频率（15%）的Vbeta和Valpha家族。在19个Vbeta库中，包括所有高频率的Vbeta，Jbeta-PCR分析显示Jbeta家族的使用受到限制，表明在广泛分布的Akta-T细胞中（除1例患者外的所有患者）对Jbeta 1亚群存在显著偏倚（65%的Akta-T细胞中Jbeta 1：Jbeta 2的平均比率为87：13）。SSCP和序列分析证实了所有患者中扩增的特异性V β-J β片段的克隆性。这些结果表明，存在克隆性扩增和限制Jbeta 1使用的T细胞在FHL是遗传相关的发病机制和免疫功能障碍的疾病。这些结果有助于解释FHL中T细胞的一些异常功能行为，并提出了有关限制克隆多样性的机制的新问题。
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare but fatal disease in infancy. There are no previous reports on the clonality of T cells in FHL patients. We analyzed here the clonality of alphabeta-T cells in 5 FHL patients using an inverse reverse transcriptase-polymerase chain reaction (RT-PCR) of the T-cell receptor variable region gene (TCR V), a joining region gene of the beta chain (Jbeta)-PCR, a single-strand conformation polymorphism (SSCP), and sequence analysis. A high frequency (15%) of Vbeta and Valpha families was observed in 3 of 5 and 4 of 4 patients examined, respectively. In 19 Vbeta repertoires, including all highly frequent Vbeta, the Jbeta-PCR analysis showed restricted usage of the Jbeta family, indicating a marked bias to Jbeta1 subsets (the mean rate of Jbeta1:Jbeta2 was 87:13 in 65% of the alphabeta-T cells) in widespread alphabeta-T cells (in all patients but 1). In all patients, the clonality of specific Vbeta-Jbeta fragment expanded was confirmed by SSCP and sequence analysis. These results suggest that the existence of clonal expansion and restricted Jbeta1 usage of T cells in FHL is genetically associated with the pathogenesis and the immunodysfunction of the disease. These results help to explain some of the abnormal functional behaviors of T cells in FHL and raise new questions regarding the mechanisms responsible for the restricted clonal diversity.