CD40 ligand upregulates expression of the IL-3 receptor and stimulates proliferation of B-lineage acute lymphoblastic leukemia cells in the presence of IL-3.
CD40 ligand upregulates expression of the IL-3 receptor and stimulates proliferation of B-lineage acute lymphoblastic leukemia cells in the presence of IL-3.
复制标题
CD40 配体上调 IL-3 受体的表达，并在 IL-3 存在的情况下刺激 B 系急性淋巴细胞白血病细胞的增殖。
DOI：
10.1038/sj.leu.2401682
复制
发表时间：
2000
期刊：
影响因子：
11.4
通讯作者：
Findley,HW
中科院分区：
文献类型：
--
作者：
Zhou,M;Gu,L;Holden,J;Yeager,AM;Findley,HW
B细胞前体急性淋巴细胞白血病（BCP-ALL）细胞对IL-3的增殖反应依赖于功能性IL-3受体（IL-3 R）的表达。在这里，我们报告，CD 40配体（CD 40 L）在重组IL-3的存在下，通过上调IL-3R的表达增加BCP-ALL细胞的增殖。早在用CD 40 L处理后1小时就观察到BCP-ALL细胞中IL-3R的上调，并且在所有研究的12例病例中检测到24小时后IL-3R表达增加50至500倍。此外，在检查的大多数BCP-ALL病例中，CD 40 L也诱导了IL-7（IL-7 R）和干细胞因子（SCF-R，c-Kit）受体的表达;然而，与IL-3R相比，诱导水平较低。为了测试IL-3、SCF和IL-7的上调受体的功能活性，我们评估了在含有CD 40 L加这些因子的无血清培养基中培养的BCP-ALL细胞的增殖和生长。当CD 40 L与单个细胞因子（IL-3、SCF和IL-7）或它们的组合一起加入时，细胞增殖显著增加，如通过DNA合成测定所检测的。CD 40 L + IL-3和SCF或IL-7的组合能够在所研究的7个病例中的3个中支持BCP-ALL细胞的长期生长至少8周。免疫表型和基因重排研究表明，长期培养的细胞是单克隆的，并保留其原始表型。白血病细胞的长期生长主要依赖于IL-3及其受体的存在，如生长因子的选择性撤回或受体的抗体阻断所示。这些结果表明，CD 40 L在上调BCP-ALL细胞上IL-3R的表达并使这些细胞在IL-3和SCF或IL-7存在下在长期培养物中增殖中起重要作用。
The proliferative response of B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells to IL-3 is dependent on the expression of functional IL-3 receptors (IL-3R). Here we report that CD40 ligand (CD40L) in the presence of recombinant IL-3 increased proliferation of BCP-ALL cells by upregulating expression of IL-3R. Upregulation of IL-3R in BCP-ALL cells was observed as early as 1 h after treatment with CD40L, and a 50-to 500-fold increase of IL-3R expression after 24 h was detected in all 12 cases studied. Moreover, expression of receptors for IL-7 (IL-7R) and stem cell factor (SCF-R, c-Kit) was also induced by CD40L in the majority of BCP-ALL cases examined; however, levels of induction were low compared to those for IL-3R. To test the functional activity of upregulated receptors for IL-3, SCF and IL-7, we evaluated the proliferation and growth of BCP-ALL cells cultured in serum-free media with CD40L plus these factors. When CD40L was added with either a single cytokine (IL-3, SCF and IL-7) or their combinations, cell proliferation was significantly increased as detected by DNA synthesis assay. Combinations of CD40L plus IL-3 and either SCF or IL-7 were able to support long-term growth of BCP-ALL cells for at least 8 weeks in three of the seven cases studied. Immunophenotyping and gene rearrangement studies indicated that cells in long-term cultures were monoclonal and retained their original phenotypes. The leukemic cells remained primarily dependent on the presence of IL-3 and its receptor for long-term growth, as shown by selective withdrawal of growth factors or antibody blockade of receptors. These results suggest an important role for CD40L in upregulating expression of IL-3R on BCP-ALL cells and enabling these cells to proliferate in long-term cultures in the presence of IL-3 and either SCF or IL-7.