Trentin L, Zambello R, Agostini C, Enthammer C, Cerutti A, Adami F, Zamboni S, Semenzato G
Padua University School of Medicine, Department of Clinical Medicine, Italy.
Blood. 1994 Dec 15;84(12):4249-56.
Leukemic cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) express tumor necrosis factor (TNF) and interleukin-2 (IL-2) receptors, but only a low proliferative response can be elicited in vitro by TNF alpha and IL-2. To investigate the functional properties of IL-2 and TNF alpha on leukemic B cells, we evaluated (1) the regulation of expression of TNF receptors (TNF-R) and IL-2 receptors on leukemic B cells after culture with TNF alpha and IL-2; (2) the effect of the combination of TNF alpha and IL-2 in a proliferative in vitro assay; and (3) the expression and regulation by these cytokines of receptors for hematopoietic factors, including IL-3, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Flow cytometry analysis showed that freshly isolated leukemic cells from B-CLL patients bear the 75-kD TNF-R and the 55-kD IL-2R; TNF alpha was able to upregulate the 55-kD IL-2R but not the 75-kD TNF-R. On the other hand, IL-2 was not able to modify the expression of the above-mentioned receptors. Although each cytokine alone was unable to induce a relevant proliferation of leukemic cells, a synergistic proliferative effect was detected when these cytokines were used in combination. Leukemic B cells from B-CLL patients bear receptors for hematopoietic factors (IL-3, G-CSF, and GM-CSF) that were upregulated in vitro by IL-2 via the 55-kD IL-2R. On the contrary, TNF alpha was unable to affect the expression of the above-mentioned receptors. These results indicate (1) that IL-2 and TNF receptors are related to each other on leukemic cells in B-CLL and (2) that the IL-2R is involved in the regulation of other structures, ie, CSF receptors, thus pointing to another functional role of this receptor complex and the related cytokine in leukemic cells.
B 细胞慢性淋巴细胞白血病（B-CLL）患者的白血病细胞表达肿瘤坏死因子（TNF）和白细胞介素-2（IL-2）受体，但体外仅能由肿瘤坏死因子α（TNFα）和 IL-2 引发低增殖反应。为研究 IL-2 和 TNFα 对白血病 B 细胞的功能特性，我们评估了：（1）用 TNFα 和 IL-2 培养后白血病 B 细胞上 TNF 受体（TNF-R）和 IL-2 受体表达的调节；（2）TNFα 和 IL-2 联合在体外增殖试验中的作用；（3）这些细胞因子对造血因子受体的表达和调节，包括 IL-3、粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）。流式细胞术分析显示，从 B-CLL 患者新鲜分离的白血病细胞带有 75-kD TNF-R 和 55-kD IL-2R；TNFα 能够上调 55-kD IL-2R，但不能上调 75-kD TNF-R。另一方面，IL-2 不能改变上述受体的表达。尽管每种细胞因子单独都不能诱导白血病细胞的相关增殖，但当这些细胞因子联合使用时，检测到协同增殖效应。B-CLL 患者的白血病 B 细胞带有造血因子（IL-3、G-CSF 和 GM-CSF）受体，IL-2 通过 55-kD IL-2R 在体外上调这些受体。相反，TNFα 不能影响上述受体的表达。这些结果表明：（1）在 B-CLL 的白血病细胞中，IL-2 和 TNF 受体相互关联；（2）IL-2R 参与其他结构即 CSF 受体的调节，从而指出该受体复合物和相关细胞因子在白血病细胞中的另一个功能作用。
