IL-2-activated lymphocytes lytic for autologous leukemia and lymphoma cells: some problems on their clinical application.

淋巴因子激活的杀伤细胞（LAK）具有广泛的杀伤肿瘤细胞的作用，但其对血液系统恶性肿瘤细胞的杀伤作用尚不清楚。本文就LAK细胞对白血病和淋巴瘤细胞的反应性进行了综述，并对LAK细胞临床应用中的一些问题进行了讨论。对白血病和淋巴瘤细胞反应的LAK细胞的诱导当来自患者和正常个体的外周血单核细胞（PBMC）与2，500 U/ml的IL-2培养5天时，超过90%的受试患者的急性白血病母细胞和淋巴瘤细胞显示出对正常供体和患者的同种异体或自体LAK细胞的溶解敏感。细胞毒性随培养时间的延长而下降.正常PBMC的裂解：正常PBMC被发现对sutherin LAK细胞的裂解敏感。B细胞和单核细胞比T淋巴细胞和NK细胞更敏感，而B细胞和T原始细胞比未刺激的对应细胞更敏感. IL-2处理的淋巴细胞对CFU-GM集落形成的抑制。骨髓CFU-GM集落形成被IL-2处理的淋巴细胞抑制.对免疫球蛋白合成的影响：在超过一半的受试供体中，IL-2处理的PBMC抑制美洲商陆有丝分裂原诱导的免疫球蛋白合成，表明IL-2.5诱导抑制细胞。染色体异常。在11名供体中，1名培养2 - 4周的PBMC出现克隆性染色体异常。综合考虑，我们目前的研究提出了使用LAK治疗的一些注意事项。我们认为，LAK细胞应用于临床试验时，需要对上述问题进行评估。

Although lymphokine-activated killer (LAK) cells have been reported to lyse broad spectrum of patients neoplastic cells, little is known on their cytotoxicity for hematological malignant cells. Here, we describe the results on LAK cells reactive against leukemia and lymphoma cells, and will discuss some problems raised when LAK cells are administered clinically.1. Induction of LAK cells reactive against leukemia and lymphoma cells.When peripheral blood mononuclear cells (PBMCs) from patients and normal individuals were cultured for 5 days with 2,500 U/ml of IL-2, acute leukemia blasts and lymphoma cells of more than 90% of patients tested were shown to be susceptible to lysis by normal donors' and patients' allogeneic or autologous LAK cells. Cytotoxicity, however, declined with the prolongation of culture periods.2. Lysis of normal PBMCs.Normal PBMCs were found to be susceptible to lysis by sutologous LAK cells. B lymhocytes and monocytes were more susceptible than T lymphocytes and NK cells, and B and T blasts were more susceptible than unstimylated counterparts.3. Inhibition of CFU-GM colony formation by IL-2-treated lymphocytes. Bone marrow-derived CFU-GM colony formation was found to be inhibited by IL-2-treated lymphocytes.4. Effect on immunoglobulin synthesis.In more than half of donors tested, IL-2-treated PBMCs inhibited pokeweed mitogen-induced immunoglobulin synthesis, suggesting the induction of suppressor cells by IL-2.5. Chromosomal abnormality.In one of 11 donors, PBMCs cultured for 2 to 4 weeks exhibited a clonal chromosome abnormality.Taken together, our present study raises some cautions as to use of LAK therapy. We think above problems need to be evaluated when LAK cells are used in clinical trials.