Cantwell M, Hua T, Pappas J, Kipps T J
Department of Medicine, UCSD School of Medicine, La Jolla, California 92093-0663, USA.
Nat Med. 1997 Sep;3(9):984-9. doi: 10.1038/nm0997-984.
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.
B细胞慢性淋巴细胞白血病（CLL）患者会出现一种免疫缺陷，其许多特征与编码CD40配体（CD154）的基因存在遗传性缺陷的人相似。我们发现，CLL患者的血液和脾脏CD4⁺ T细胞在CD3连接后无法表达表面CD154。然而，使用基于酶联免疫吸附测定（ELISA）的定量竞争性聚合酶链反应（PCR），我们注意到CD3连接可诱导此类T细胞表达CD154信使核糖核酸，其水平与正常供体的CD3激活T细胞相似。此外，向活化的正常供体T细胞中添加越来越多的CLL B细胞会迅速导致CD154的下调程度逐渐增大。在体外培养物中添加CD40单克隆抗体可阻断CD154的这种下调。我们提出，白血病细胞介导的活化T细胞上CD154的下调是CLL患者某些获得性免疫缺陷的原因。
