Kay N E, Han L, Bone N, Williams G
Mayo Clinic, 200 First Street SW, Rochester, NY 55905, USA.
Br J Haematol. 2001 Mar;112(3):760-7. doi: 10.1046/j.1365-2141.2001.02605.x.
B-chronic lymphocytic leukaemia (CLL) clonal B cells are characterized by resistance to apoptosis. We evaluated clonal B cells and blood T cells for interleukin 4 (IL-4) content as IL-4 is able to increase CLL cell resistance to apoptosis. The content of IL-4 in CD8+ T cells of CLL patients (n = 9) ranged from 37% to 63% of the total CD8+ T cells (mean level of 49% +/- 3.4) compared with a range of 5-10% for control CD8+ T cells. Clonal B cells positive for cytoplasmic IL-4 ranged from 1% to 97% (mean value 57.8 +/- 6.9%). CD8+ T cells and clonal B cells secreted detectable levels of IL-4, but only clonal CLL B cells (n = 4) secreted IL-4 in association with increasing cell numbers. Fludarabine (F-ara-AMP, 0.1-100 micromol/ml) was able to downregulate the IL-4 content of CD8+ T cells, but not clonal B-cell IL-4. Culture supernatant from CLL CD8+ T cells decreased the spontaneous apoptotic rate of clonal B cells that was reversed with anti-IL-4 and soluble IL-4 receptor. These findings show that IL-4 is present in the microenvironment of B-CLL. In addition, use of agents that can interfere with IL-4 presentation to clonal B cells can be effective in increasing clonal B-cell apoptosis.
B 细胞慢性淋巴细胞白血病（CLL）的克隆性 B 细胞具有抗凋亡特性。由于白细胞介素 4（IL-4）能够增强 CLL 细胞的抗凋亡能力，我们对克隆性 B 细胞和血液 T 细胞中的 IL-4 含量进行了评估。CLL 患者（n = 9）的 CD8⁺T 细胞中，IL-4 含量占总 CD8⁺T 细胞的 37%至 63%（平均水平为 49%±3.4%），而对照 CD8⁺T 细胞的这一范围为 5%至 10%。细胞质 IL-4 呈阳性的克隆性 B 细胞比例为 1%至 97%（平均值为 57.8%±6.9%）。CD8⁺T 细胞和克隆性 B 细胞均分泌可检测水平的 IL-4，但只有克隆性 CLL B 细胞（n = 4）随着细胞数量增加而分泌 IL-4。氟达拉滨（F-ara-AMP，0.1 - 100 μmol/ml）能够下调 CD8⁺T 细胞中的 IL-4 含量，但对克隆性 B 细胞的 IL-4 含量无影响。CLL CD8⁺T 细胞的培养上清液降低了克隆性 B 细胞的自发凋亡率，而抗 IL-4 和可溶性 IL-4 受体可逆转这一作用。这些发现表明，IL-4 存在于 B-CLL 的微环境中。此外，使用能够干扰 IL-4 作用于克隆性 B 细胞的药物，可能有效增加克隆性 B 细胞的凋亡。
