Genot E, Sarfati M, Sigaux F, Petit-Koskas E, Billard C, Mathiot C, Falcoff E, Delespesse G, Kolb J P
U.196 INSERM Recherche sur les interférons, Institut Curie, Paris, France.
Blood. 1989 Nov 15;74(7):2455-63.
Hairy cells are stimulated to DNA synthesis by low molecular weight B cell growth factor (LMW-BCGF) and this proliferative response is suppressed by interferon (IFN)-alpha, both in vitro and in vivo. The suggestion that the CD23 molecule (Fc epsilon II receptor) might be involved in the signalling pathway of LMW-BCGF prompted us to study the expression of this molecule on hairy cells and its modulation by IFN-alpha. By flow cytometry and direct binding experiments with anti CD23 monoclonal antibodies, the presence of the CD23 antigen was detected in 7 of 12 cases tested, on variable percentages of cells, ranging from low to medium expression. In vitro incubation of hairy cells with IFN-alpha, which elicits a suppression of the proliferative response of these cells to LMW-BCGF, induced a parallel significant reduction of CD23 expression in only three cases. Similarly, a transient in vivo decrease of CD23 expression, concommitant with an inhibition of the LMW-BCGF response, could be detected in only one of three patients injected with IFN-alpha. Soluble sCD23/IgE-binding factor (BF) was quantitated in the serum from six other patients with hyperleukocytic hairy cell leukemia (HCL) undergoing a clinical trial of IFN-alpha therapy. Before treatment, these patients presented higher concentrations of the cleaved soluble form of the CD23 molecule than normal controls. Within a few weeks of IFN-alpha administration, these levels markedly decreased, paralleling a diminution of blood leukemic cells. Of interest, no such diminution was noticed for another patient resistant to IFN-alpha therapy. These results show that the proliferative response of hairy cells to LMW-BCGF is not linked to the expression of the CD23 marker. Besides, when the latter molecule was present, its decrease following IFN-alpha treatment, which could be detected in some cases, was not necessarily required for the suppression of the LMW-BCGF response and is thus not mandatory for the therapeutic efficacy of IFN-alpha. Our results point out that quantitation of serum sCD23/IgE-BF, whether related to a process of autocrine proliferation or not, is a parameter of potential importance for therapy monitoring.
毛细胞可被低分子量B细胞生长因子（LMW - BCGF）刺激进行DNA合成，且这种增殖反应在体外和体内均受到α干扰素（IFN）的抑制。关于CD23分子（FcεII受体）可能参与LMW - BCGF信号通路的推测促使我们研究该分子在毛细胞上的表达及其受α干扰素的调节情况。通过流式细胞术以及使用抗CD23单克隆抗体的直接结合实验，在12例受试病例中的7例检测到了CD23抗原的存在，其在不同比例的细胞上表达，表达水平从低到中等。用α干扰素体外培养毛细胞，这会抑制这些细胞对LMW - BCGF的增殖反应，但仅在3例中诱导了CD23表达的平行显著降低。同样，在3例注射α干扰素的患者中，仅1例检测到CD23表达的短暂体内降低，同时伴有LMW - BCGF反应的抑制。对另外6例接受α干扰素治疗临床试验的高白细胞性毛细胞白血病（HCL）患者的血清中可溶性sCD23/IgE结合因子（BF）进行了定量分析。治疗前，这些患者血清中CD23分子裂解的可溶性形式的浓度高于正常对照。在给予α干扰素后的几周内，这些水平显著下降，与血液中白血病细胞数量的减少平行。有趣的是，另一位对α干扰素治疗耐药的患者未观察到这种下降。这些结果表明，毛细胞对LMW - BCGF的增殖反应与CD23标志物的表达无关。此外，当存在后者分子时，α干扰素治疗后其减少（在某些情况下可检测到）对于抑制LMW - BCGF反应并非必需，因此对于α干扰素的治疗效果也不是必需的。我们的结果指出，血清sCD23/IgE - BF的定量分析，无论是否与自分泌增殖过程相关，都是治疗监测中一个潜在重要的参数。
