Chang W C, Fujimiya Y, Casteel N, Pattengale P
Department of Pathology, Children's Hospital of Los Angeles, CA 90027.
Int J Cancer. 1989 Apr 15;43(4):591-7. doi: 10.1002/ijc.2910430410.
Even though they possess normal to increased numbers of circulating natural killer (NK) cells, patients with chronic myelogenous leukemia (CML) have a functional NK-cell deficiency which is restorable in vitro in the presence of recombinant IL-2. We therefore measured the level of IL-2 production by both T-helper and NK cells from CML patients as compared to normal controls using PHA-stimulated peripheral blood mononuclear cells (PBMs) as well as FACS-sorted CD4+ (OKT4+) lymphoid cells and FACS-sorted CD16+ (B73.1+) lymphoid cells. Peripheral blood mononuclear cells from CML patients demonstrated markedly defective IL-2 production as compared to normal controls (4.0 +/- 1.6 and 5.9 +/- 1.4 units/ml after 24 hr of 5 and 10 micrograms/ml PHA stimulation as compared with 40.7 +/- 10.3 and 69.3 +/- 15.1 units/ml for normal subjects). In addition to the decreased relative percentage of CD4+ (OKT4+) lymphoid cells in CML patients, FACS-sorted CD4+ (OKT4+) cells also demonstrated a significant defect in IL-2 production, (10.8 +/- 3.6 units/ml as compared to 39.0 +/- 5.8 units/ml after 24 hr stimulation with 10 micrograms/ml PHA). FACS-sorted CD16+ (B73.1+) lymphoid cells from CML patients also demonstrated significantly decreased IL-2 production after 24 hr incubation with increasing concentrations of PHA or with the NK-sensitive target K562 as compared to normal controls. Defective IL-2 production by PBMs, CD4+ (OKT4+), and CD16+ (B73.1+) cells from CML patients was also evident after 48 hr of PHA stimulation. Although the percentages of both T4+2H4+ and T4+4B4+ subsets are significantly decreased in CML patients, CML patients have normal ratios of T4+4B4+/T4+2H4+ subsets as compared to normal controls. These and previous results support the hypothesis that decreased IL-2 production by both T-helper and NK cells from CML patients may be mechanistically related to the observed NK-cell immunodeficiency in CML patients.
尽管慢性粒细胞白血病（CML）患者循环中的自然杀伤（NK）细胞数量正常或增加，但他们存在功能性NK细胞缺陷，在重组白细胞介素-2（IL-2）存在的情况下，这种缺陷在体外是可恢复的。因此，我们使用PHA刺激的外周血单个核细胞（PBMs）以及流式细胞术分选的CD4 +（OKT4 +）淋巴细胞和流式细胞术分选的CD16 +（B73.1 +）淋巴细胞，测量了CML患者与正常对照相比，T辅助细胞和NK细胞产生IL-2的水平。与正常对照相比，CML患者的外周血单个核细胞显示出明显的IL-2产生缺陷（5和10μg/ml PHA刺激24小时后分别为4.0±1.6和5.9±1.4单位/ml，而正常受试者为40.7±10.3和69.3±15.1单位/ml）。除了CML患者中CD4 +（OKT4 +）淋巴细胞的相对百分比降低外，流式细胞术分选的CD4 +（OKT4 +）细胞在IL-2产生方面也显示出明显缺陷（10μg/ml PHA刺激24小时后为10.8±3.6单位/ml，而正常对照为39.0±5.8单位/ml）。与正常对照相比，CML患者的流式细胞术分选的CD16 +（B73.1 +）淋巴细胞在与浓度增加的PHA或NK敏感靶细胞K562孵育24小时后，IL-2产生也显著降低。PHA刺激48小时后，CML患者的PBMs、CD4 +（OKT4 +）和CD16 +（B73.1 +）细胞的IL-2产生缺陷也很明显。尽管CML患者中T4 + 2H4 +和T4 + 4B4 +亚群的百分比均显著降低，但与正常对照相比，CML患者T4 + 4B4 + /T4 + 2H4 +亚群的比例正常。这些结果以及先前的结果支持这样的假设，即CML患者的T辅助细胞和NK细胞产生IL-2的减少可能与CML患者中观察到的NK细胞免疫缺陷在机制上相关。
