Jewell A P, Worman C P, Giles F J, Goldstone A H, Lydyard P M
Department of Haematology, University College, Middlesex School of Medicine, London, U.K.
Leuk Lymphoma. 1992 Aug;7(5-6):473-80. doi: 10.3109/10428199209049804.
Recent studies have shown that, when used in early stage disease, interferon-alpha (IFN-alpha) can produce a fall in the number of malignant cells in the peripheral blood of patients with B-CLL. In this study, we investigated the effect of IFN-alpha on natural killer (NK) cell and lymphokine-activated cell (LAK) activity in patients with B-CLL. In vitro, IFN-alpha (500 U/ml for 18 hours) induced LAK activity in patients with B-CLL (27.7 +/- 9.9%, n = 20), and IL-2 (500 U/ml for 5 days) produced similar activity (35.9 +/- 8.8%, n = 7). Despite the induction of LAK activity by IFN-alpha and IL2 in patients with B-CLL, the malignant cells remained resistant to both allogeneic and autologous LAK effectors. NK activity in patients with B-CLL is also low (23.1 +/- 7.2%, n = 20), and B-CLL cells were resistant to NK cell activity. In cold target competition assays, CLL cells did not compete with labelled K562 or Daudi targets in the NK and LAK assays, suggesting that the malignant cells are not recognised by the effector cells, and this may be related to low level of expression of the adhesion receptors, LFA-1 and ICAM-1. Finally, CLL cells were also resistant to antibody dependent cell mediated cytotoxicity, but were susceptible to antibody dependent complement mediated lysis. These results suggest that it is unlikely that the effects of IFN-alpha in B-CLL are due to the enhancement of NK or LAK activity.
近期研究表明，α干扰素（IFN-α）用于疾病早期时，可使B细胞慢性淋巴细胞白血病（B-CLL）患者外周血中的恶性细胞数量减少。在本研究中，我们调查了IFN-α对B-CLL患者自然杀伤（NK）细胞和淋巴因子激活细胞（LAK）活性的影响。在体外，IFN-α（500 U/ml，作用18小时）可诱导B-CLL患者产生LAK活性（27.7±9.9%，n = 20），白细胞介素-2（IL-2，500 U/ml，作用5天）也可产生类似活性（35.9±8.8%，n = 7）。尽管IFN-α和IL-2可诱导B-CLL患者产生LAK活性，但恶性细胞对同种异体和自体LAK效应细胞均具有抗性。B-CLL患者的NK活性也较低（23.1±7.2%，n = 20），且B-CLL细胞对NK细胞活性具有抗性。在冷靶竞争试验中，CLL细胞在NK和LAK试验中不与标记的K562或Daudi靶细胞竞争，这表明效应细胞无法识别恶性细胞，这可能与黏附受体LFA-1和ICAM-1的低表达水平有关。最后，CLL细胞对抗体依赖性细胞介导的细胞毒性也具有抗性，但对抗体依赖性补体介导的裂解敏感。这些结果表明，IFN-α对B-CLL的作用不太可能是由于NK或LAK活性增强所致。
