Voogt P J, Falkenburg J H, Fibbe W E, Veenhof W F, Hamilton M, Van Krimpen B A, Bolhuis R L
Department of Hematology, University Medical Center, Leiden, The Netherlands.
J Immunol. 1989 Mar 1;142(5):1774-80.
To evaluate the capability of NK cells and cytotoxic T lymphocytes to interact with normal hematopoietic progenitor cells (HPC), as compared to neoplastic lymphohematopoietic cells, we investigated inhibition of colony growth of these cell populations in semi-solid culture systems, after incubation with cloned cytotoxic effector cells. Three different types of cloned effector cells were investigated: TCR-/CD3- NK cells, TCR-gamma delta+/CD3+ cells, and TCR-alpha beta+/CD3+ cytotoxic T lymphocytes. Effector cells showed differential levels of tumor cell colony inhibition, but no MHC-non-restricted lysis of normal HPC was observed. Pre-stimulation of normal HPC by culturing on established stromal layers had no effect. Cell-mediated lysis of HPC only occurred by Ag-specific MHC-restricted lysis by CTL, or by antibody-dependent cellular cytotoxicity. In cell mixing experiments, irradiated tumor cells, but not normal bone marrow cells inhibited tumor cell lysis. Furthermore, cloned effector lymphocytes were able to specifically eliminate malignant cells from tumor contaminated bone marrow without damaging normal HPC. When fresh leukemic cells were used as targets, growth of acute myeloblastic leukemia colonies was inhibited after incubation with several cytotoxic effector clones, whereas chronic myeloid leukemia precursor cells showed limited sensitivity to MHC-non-restricted cytolysis. These results indicate that MHC-non-restricted cytolysis by NK cells is selectively directed against neoplastic cells and not against normal HPC.
为了评估自然杀伤细胞（NK 细胞）和细胞毒性 T 淋巴细胞与正常造血祖细胞（HPC）相互作用的能力，并与肿瘤性淋巴造血细胞进行比较，我们在与克隆的细胞毒性效应细胞孵育后，研究了这些细胞群体在半固体培养系统中集落生长的抑制情况。研究了三种不同类型的克隆效应细胞：TCR-/CD3- NK 细胞、TCR-γδ+/CD3+细胞和 TCR-αβ+/CD3+细胞毒性 T 淋巴细胞。效应细胞对肿瘤细胞集落的抑制水平存在差异，但未观察到对正常 HPC 的 MHC 非限制性裂解。在已建立的基质层上培养对正常 HPC 进行预刺激没有效果。HPC 的细胞介导裂解仅通过 CTL 的 Ag 特异性 MHC 限制性裂解或通过抗体依赖性细胞毒性发生。在细胞混合实验中，经照射的肿瘤细胞而非正常骨髓细胞抑制了肿瘤细胞裂解。此外，克隆的效应淋巴细胞能够特异性地从肿瘤污染的骨髓中清除恶性细胞，而不损害正常 HPC。当使用新鲜白血病细胞作为靶标时，与几种细胞毒性效应克隆孵育后，急性髓性白血病集落的生长受到抑制，而慢性髓性白血病前体细胞对 MHC 非限制性细胞溶解的敏感性有限。这些结果表明，NK 细胞的 MHC 非限制性细胞溶解选择性地针对肿瘤细胞，而非正常 HPC。
