Acquired CD40-ligand deficiency in chronic lymphocytic leukemia
Acquired CD40-ligand deficiency in chronic lymphocytic leukemia
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DOI：
10.1038/nm0997-984
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发表时间：
1997-09-01
期刊：
影响因子：
82.9
通讯作者：
Kipps, TJ
中科院分区：
文献类型：
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作者：
Cantwell, M;Hua, T;Kipps, TJ
B细胞慢性淋巴细胞白血病（CLL）患者获得的免疫缺陷具有许多特征，与编码CD40配体（CD154）的基因存在遗传缺陷的人相似。我们发现CLL患者的血液和脾脏CD4（+）T细胞在CD3结扎后不能表达表面CD154。然而，使用酶联免疫吸附试验（ELISA）为基础的定量竞争性聚合酶链反应（PCR），我们注意到，CD3连接可以诱导这样的T细胞表达CD154信使RNA的水平类似于正常供体的CD3激活的T细胞。此外，将增加数量的CLL B细胞添加到活化的正常供体T细胞中迅速导致CD 154的逐渐更大的下调。这种下调的CD154可以通过在体外培养物中加入CD40单克隆抗体来阻断。我们认为，白血病细胞介导的下调活化T细胞上的CD154是导致CLL患者获得性免疫缺陷的原因。
Patients with B-cell chronic lymphocytic leukemia (CLL) acquire an immunodeficiency with many characteristics similar to those of persons with inherited defects in the gene encoding the CD40-ligand (CD154). We found that the blood and splenic CD4(+) T cells of patients with CLL failed to express surface CD154 after CD3 ligation. However, using an enzyme-linked immunosorbent assay (ELISA)-based quantitative competitive polymerase chain reaction (PCR), we noted that CD3 ligation could induce such T cells to express CD154 messenger RNA at levels similar to that of CD3-activated T cells from normal donors. Moreover, addition of Increasing numbers of CLL B cells to activated normal donor T cells rapidly resulted in progressively greater down-modulation of CD154. Such down-modulation of CD154 could be blocked by addition of CD40 monoclonal antibody to cultures in vitro. We propose that leukemia cell-mediated down-modulation of CD154 on activated T cells accounts for some of the acquired immune defects of patients with CLL.