Immunostimulatory CpG-oligonucleotides induce functional high affinity IL-2 receptors on B-CLL cells: Costimulation with IL-2 results in a highly immunogenic phenotype
Immunostimulatory CpG-oligonucleotides induce functional high affinity IL-2 receptors on B-CLL cells: Costimulation with IL-2 results in a highly immunogenic phenotype
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DOI：
10.1016/s0301-472x(00)00144-2
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发表时间：
2000-05-01
影响因子：
2.6
通讯作者：
Peschel, C
中科院分区：
文献类型：
--
作者：
Decker, T;Schneller, F;Peschel, C
Objective. CpG-寡脱氧核苷酸（CpG-ODN）在正常和恶性的人B细胞中具有诱导增殖、细胞因子产生和表面分子调节的作用。在本研究中，我们研究了CpG-ODN在白血病和正常B细胞中诱导功能性高亲和力受体的潜力，以及与IL-2共刺激对增殖、细胞因子分泌和表面分子调节的影响。用含或不含IL-2的CpG-ODN刺激高度纯化的B-CLL患者和正常对照的B细胞，流式细胞仪检测CD 25的表达，Scatchard分析检测高亲和力IL-2受体的存在。使用增殖测定、ELISA（IL-6、TNF-α）和FAGS分析（CD 80、CD 86表达）研究IL-2和CpG-ODN的共刺激作用。在混合淋巴细胞反应和干扰素-γ Elispot测定中确定自体和同种异体T细胞对活化的B-CLL细胞的反应性。结果，与正常B细胞相比，CpG-ODN DSP 30对恶性肿瘤中IL-2受体α链的诱导作用明显更强（p = 0.03）。这导致在B-CLL细胞中表达功能性高亲和力IL-2受体，但在正常R细胞中表达较少数量的具有较低亲和力的受体。虽然加入IL-2的CpC-ODN刺激的细胞在正常B细胞和B-CLL细胞中的增殖增加，但在正常B细胞中未观察到对细胞因子产生或表面分子表达的共刺激作用。相反，TNF-α和IL-6的产生在B-CLL细胞中增加，并且当IL-2用作共刺激物时，CD 80和CD 86的表达进一步增强。CpG-ODN和IL-2联合刺激的B-CLL细胞的自体免疫和同种异体免疫识别能力较CpG-ODN单独刺激的B-CLL细胞增强。用CpG-ODN和IL-2刺激B-CLL细胞可能是B-CLL患者潜在免疫治疗的有吸引力的策略。(C)2000年国际实验血液学学会。爱思唯尔科学公司出版
Objective. CpG-oligodeoxynucleotides (CpG-ODN) have been shown to induce proliferation, cytokine production, and surface molecule regulation in normal and malignant human B cells. In the present study, we investigated the potential of CpG-ODN to induce functional high-affinity receptors in leukemic and normal B cells and the effects of costimulation with IL-2 on proliferation, cytokine secretion, and surface molecule regulation.Methods. Highly purified B cells from B-CLL patients and normal controls cr ere stimulated with CpG-ODN with or without IL-2, Expression of CD25 was determined using FACS, and the presence of high-affinity IL-2 receptors was determined by scatchard analysis. Costimulatory effects of IL-2 and CpG-ODN were investigated using proliferation assays, ELISA (IL-6, TNF-alpha), and FAGS analysis (CD80, CD86 expression). Reactivity of autologous and allogeneic T cells toward activated B-CLL cells was determined in mixed lymphocyte reactions and interferon-gamma Elispot assays.Results, The CpG-ODN DSP30 caused a significantly stronger induction of the IL-2 receptor alpha chain in malignant as compared with normal B cells (p = 0.03). This resulted in the expression of functional high-affinity IL-2 receptors in B-CLL cells, but fewer numbers of receptors with Less affinity were expressed in normal R cells. Although addition of IL-2 to CpC-ODN-stimulated cells augmented proliferation in both normal B cells and B-CLL cells, no costimulatory effect on cytokine production or surface molecule expression could be observed in normal B cells. In contrast, TNF-alpha and IL-6 production was increased in B-CLL cells, and the expression of CD80 and CD86 was further enhanced when IL-2 was used as a costimulus. Autologous and allogeneic immune recognition of B-CLL cells stimulated with CpG-ODN and IL-2 was increased compared with B-CLL cells stimulated with CpG-ODN alone.Conclusion. Stimulation of B-CLL cells with CpG-ODN and IL-2 might be an attractive strategy for potential immunotherapies for B-CLL patients. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.