Kluin-Nelemans J C, Kester M G, Oving I, Cluitmans F H, Willemze R, Falkenburg J H
Laboratory of Experimental Hematology, University Medical Center, Leiden, The Netherlands.
Leukemia. 1994 Dec;8(12):2095-101.
Hairy-cell leukemia (HCL) is a B-cell leukemia, but many factors argue for a T-cell dysfunction and/or involvement in this disease. Hairy cells typically home in the spleen, and become circulating only late in the disease. As it is assumed that the T-cell abnormalities are caused by specific interactions with the hairy cells, we studied the immunophenotype in 17 cases (CD3, CD4, CD8, CD45R0, TCR gamma delta) and cytokine gene expression in four cases (IL-1 beta, IL-2, IL-3, IL-4, IL-6, IL-7, IL-10, IFN-gamma, TNF-alpha, GM-CSF and the receptors of IL-1 and IL-2, using the cDNA-PCR technique) of purified T-cell fractions from hairy-cell spleens. By Northern blot analysis, mRNA for IFN-gamma, GM-CSF, IL-10 and TNF-alpha was measured in purified T cells and hairy cells from three HCL spleens. The results of the immunophenotype and cDNA-PCR data were compared with ten normal spleens. Compared to blood, splenic T cells showed a reversed CD4/CD8 ratio, a normal percentage of memory T cells, and an increase in CD3+TCR gamma delta + cells. Without specific induction spontaneous cytokine gene expression of IL-2, IL-4, IFN-gamma, and GM-CSF was seen in the purified T-cell fractions without signals in the purified hairy-cell fractions. mRNA expression of IFN-gamma and GM-CSF in the T cells, and of IL-10 and TNF-alpha in the hairy cells was confirmed by the Northern blot technique. From these data we suggest that splenic T cells in HCL should not be considered as residual or recirculating T cells, but rather as tumor-infiltrating lymphocytes.
毛细胞白血病(HCL)是一种B细胞白血病,但许多因素表明T细胞功能障碍和/或参与了这种疾病。毛细胞通常定居于脾脏,仅在疾病晚期才进入血液循环。由于假定T细胞异常是由与毛细胞的特定相互作用引起的,我们研究了17例患者的免疫表型(CD3、CD4、CD8、CD45R0、TCRγδ),并使用cDNA-PCR技术研究了4例患者纯化的T细胞组分中细胞因子基因的表达情况(IL-1β、IL-2、IL-3、IL-4、IL-6、IL-7、IL-10、IFN-γ、TNF-α、GM-CSF以及IL-1和IL-2的受体),这些细胞组分来自毛细胞脾脏。通过Northern印迹分析,检测了来自三个HCL脾脏的纯化T细胞和毛细胞中IFN-γ、GM-CSF、IL-10和TNF-α的mRNA。将免疫表型和cDNA-PCR数据的结果与十个正常脾脏进行了比较。与血液相比,脾脏T细胞显示CD4/CD8比值倒置、记忆T细胞百分比正常以及CD3+TCRγδ +细胞增加。在没有特异性诱导的情况下,纯化的T细胞组分中可见IL-2、IL-4、IFN-γ和GM-CSF的自发细胞因子基因表达,而纯化的毛细胞组分中无信号。通过Northern印迹技术证实了T细胞中IFN-γ和GM-CSF以及毛细胞中IL-10和TNF-α的mRNA表达。根据这些数据,我们认为HCL中的脾脏T细胞不应被视为残留或再循环的T细胞,而应被视为肿瘤浸润淋巴细胞。