Zambello R, Cassatella M A, Trentin L, Bulian P, Siviero F, Feruglio C, Agostini C, Vespignani M, Chisesi T, Pizzolo G
Department of Clinical Medicine, University of Padua, Italy.
Leukemia. 1991 Nov;5(11):942-50.
To investigate the role of p55 and p75 chains of interleukin-2 receptor (IL-2R) on the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), the cells obtained from 11 LDGL patients (belonging to the CD3+ group) were studied for (a) the surface expression and (b) mRNA transcripts of the p55 and p75 IL-2R after activation with anti-CD3 monoclonal antibody (mAb) or interleukin-2 (IL-2). The effects of mAbs specifically blocking the p55 and p75 IL-2R on the generation of proliferative and cytotoxic functions were studied following anti-CD3 mAb stimulation. A significant difference was observed in the expression of p55 and p75 antigens on LDGL cells under resting conditions: a low number of p55 IL-2R+ (mean 1.2 +/- 0.4%) and high values of p75 IL-2R+ cells (54.9 +/- 7.4%). Accordingly, a barely detectable message for the p55 IL-2R and a strong signal for the p75 IL-2R mRNA were demonstrated. Following activation with anti-CD3 or IL-2, different patterns of IL-2R expression were observed. Anti-CD3 mAb induced an increase in the expression of the p55 IL-2R both at the mRNA and antigen level, whereas the p75 values remained consistently raised. In contrast, IL-2 induced the expression of p55 IL-2R mRNA associated with only a slight expression of this antigen. This finding was associated with a decrease in the cell expression of the p75 IL-2R, whereas the amount of p75 mRNA was unchanged. Both anti-CD3 mAb and IL-2 induced cell proliferation and cytotoxicity against the K-562 target cells. Anti-p55 IL-2R mAb did not affect the cytotoxic activity mediated by anti-CD3, but it markedly inhibited cell proliferation. Anti-p75 mAb did not inhibit either lytic function or cell proliferation mediated by anti-CD3 mAb, suggesting that only the high affinity IL-2R (p55 plus p75) is involved in anti-CD3 mediated cell activation in LDGL patients. This mechanism is different from that responsible for the IL-2 activation of CD3+ GL in LDGL patients, which is achieved through the p75 IL-2R alone. These results provide new insights into the pathophysiology of proliferating GL in LDGL patients and may also contribute to further characterization of the normal CD3+ GL population.
为研究白细胞介素-2受体（IL-2R）的p55和p75链在颗粒淋巴细胞增殖性疾病（LDGL）患者中对颗粒淋巴细胞（GL）激活的作用，对11例LDGL患者（属于CD3+组）的细胞进行了研究，观察其在用抗CD3单克隆抗体（mAb）或白细胞介素-2（IL-2）激活后（a）p55和p75 IL-2R的表面表达及（b）mRNA转录本情况。在抗CD3 mAb刺激后，研究了特异性阻断p55和p75 IL-2R的mAb对增殖和细胞毒性功能产生的影响。观察到在静息状态下LDGL细胞上p55和p75抗原的表达存在显著差异：p55 IL-2R+细胞数量少（平均1.2±0.4%），而p75 IL-2R+细胞值高（54.9±7.4%）。相应地，p55 IL-2R的信息几乎检测不到，而p75 IL-2R mRNA有强烈信号。在用抗CD3或IL-2激活后，观察到不同的IL-2R表达模式。抗CD3 mAb在mRNA和抗原水平均诱导p55 IL-2R表达增加，而p75值持续升高。相比之下，IL-2诱导p55 IL-2R mRNA表达，而该抗原仅有轻微表达。这一发现与p75 IL-2R的细胞表达减少相关，而p75 mRNA量未改变。抗CD3 mAb和IL-2均诱导细胞增殖及对K-562靶细胞的细胞毒性。抗p55 IL-2R mAb不影响抗CD3介导的细胞毒性活性，但显著抑制细胞增殖。抗p75 mAb既不抑制抗CD3 mAb介导的裂解功能也不抑制细胞增殖，这表明在LDGL患者中只有高亲和力IL-2R（p55加p75）参与抗CD3介导的细胞激活。该机制不同于LDGL患者中CD3+ GL的IL-2激活机制，后者仅通过p75 IL-2R实现。这些结果为LDGL患者中增殖性GL的病理生理学提供了新见解，也可能有助于进一步明确正常CD3+ GL群体的特征。
