Sahraoui Y, Allouche M, Ammar A, Spanakis E, Clemenceau C, Jasmin C, Perraki M, Varela-Millot C, Georgoulias V
Oncogénèse Appliquée, INSERM U268, Hôpital Paul Brousse, Villejuif, France.
Leukemia. 1992 Oct;6(10):1025-35.
In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti-IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells.
为了确定白细胞介素2（IL2）在T细胞急性淋巴细胞白血病（T-ALL）患者白血病细胞增殖中的作用，我们研究了IL2的产生、T-ALL细胞上表达的IL2受体（IL2R）的功能及其IL-2依赖的体外增殖。17例T-ALL/T细胞非霍奇金淋巴瘤患者中，6例白血病细胞具有原胸腺细胞（I期）或成熟胸腺细胞（III期）表型，但不具有普通胸腺细胞（II期）表型，这些白血病细胞能够以剂量依赖的方式对重组IL2（rIL2）、抗Tac和TU27单克隆抗体作出反应而增殖，多克隆抗IL2纯化免疫球蛋白G可抑制这种IL2诱导的细胞增殖。通过比色生物学和免疫酶测定评估，13例受试患者中有10例患者的T-ALL细胞条件培养基（粗提或/和经Amicon浓缩）含有IL2活性；这种生物活性归因于免疫亲和测定中被抗IL2抗体吸附的14.5 kDa分子。尽管新鲜白血病细胞中表达IL2Rα（Tac）链的细胞不到10%，但在无任何促有丝分裂刺激的情况下进行24小时细胞培养后，13例患者中有5例（11%-83%的Tac+细胞）诱导了IL2Rα链的表达。此外，在所有10例受试患者的新鲜细胞中均可检测到Tac mRNA转录本。用IL-2Rβ链特异性单克隆抗体对新鲜白血病细胞进行染色并通过流式细胞术分析显示，4%-13%的白血病细胞呈阳性。用125I-rIL2进行的结合实验表明，3例T-ALL患者的新鲜细胞上有少量高亲和力IL2R（114-200个位点/细胞，解离常数=101-181 pm）。最后，抗IL2Rα、抗IL2Rβ和抗IL2抗体可抑制大多数患者T-ALL细胞的IL2驱动和自发细胞增殖，尽管在某些情况下观察到了异质性抑制模式。综上所述，这些发现强烈提示IL2/IL2R依赖机制可能参与了某些T-ALL细胞的增殖。
