Gressler V H, Weinkauff R E, Franklin W A, Golomb H M
Department of Medicine, University of Chicago, IL 60637.
Blood. 1988 Sep;72(3):1048-53.
The mechanism of action responsible for the beneficial effect of alpha-interferon (alpha-IFN) in patients with hairy cell leukemia (HCL) is still unknown. Direct antineoplastic and immunomodulating effects on both the host immune system and the hairy cells themselves have been implicated. To evaluate whether lymphokines have any regulatory effect on antigens of the major histocompatibility complex (MHC) on hairy cells and whether this corresponds to prognostic clinical parameters, we studied splenic hairy cells from ten previously untreated patients. The samples were incubated with recombinant human alpha-IFN, gamma-IFN (gamma-IFN), and interleukin-2 (IL-2). In an indirect staining procedure, cells were labeled with monoclonal antibodies (MoAb) to HLA ABC and HLA DR surface structures and subjected to cytofluorimetric analysis. Results concerning the expression of MHC class I and HLA DR antigens were mixed for incubation of hairy cells with gamma-IFN and IL-2, whereas alpha-IFN had a distinct effect on HLA DR antigen expression. alpha-IFN strongly enhanced the intensity of staining with HLA DR MoAb in six patients, and it increased the percentage of MoAb-positive cells in five of these samples. In contrast, the staining intensity in samples from four patients was reduced considerably on alpha-IFN treatment. In this group, two samples showed a sharp alpha-IFN-induced decrease in the number of HLA DR MoAb-positive cells from originally high values, and in one sample the very low percentage of positive cells was unaffected by alpha-IFN exposure. These two groups of patients whose hairy cells displayed contrasting HLA DR expression on incubation with alpha-IFN in vitro, were found to differ in their subsequent clinical course.
α干扰素(α-IFN)对毛细胞白血病(HCL)患者产生有益作用的作用机制尚不清楚。其对宿主免疫系统和毛细胞本身的直接抗肿瘤及免疫调节作用已被提及。为了评估淋巴因子对毛细胞上主要组织相容性复合体(MHC)抗原是否有任何调节作用,以及这是否与临床预后参数相关,我们研究了10例未经治疗患者的脾脏毛细胞。将样本与重组人α-IFN、γ-IFN(γ-IFN)和白细胞介素-2(IL-2)一起孵育。在间接染色过程中,用针对HLA ABC和HLA DR表面结构的单克隆抗体(MoAb)标记细胞,并进行细胞荧光分析。关于MHC I类和HLA DR抗原表达的结果在毛细胞与γ-IFN和IL-2孵育时各异,而α-IFN对HLA DR抗原表达有明显影响。α-IFN使6例患者中HLA DR MoAb的染色强度显著增强,并且在其中5个样本中增加了MoAb阳性细胞的百分比。相反,4例患者样本在α-IFN处理后染色强度大幅降低。在该组中,2个样本显示α-IFN诱导HLA DR MoAb阳性细胞数量从原本的高值急剧下降,并且在1个样本中,极低百分比的阳性细胞不受α-IFN暴露的影响。发现这两组在体外与α-IFN孵育时毛细胞显示出对比性HLA DR表达的患者,其后续临床病程有所不同。