Main E K, Lampson L A, Hart M K, Kornbluth J, Wilson D B
J Immunol. 1985 Jul;135(1):242-6.
The susceptibility of human neuroblastoma cells to direct cellular cytotoxicity has not been previously established. This is of particular interest because of their aggressive growth and low HLA expression. Neuroblastoma lines CHP 100 and CHP 126 were found to be excellent targets in 4-hr CML assays. Natural killer (NK) cells from fresh PBL and from an NK clone, 3.3, have high lytic activity against both cell lines. We also studied mixed lymphocyte culture-generated cytotoxic lines containing allo-specific cytotoxic T lymphocytes (CTL) directed against HLA antigens present on the neuroblastoma target cell lines. These lines did show excellent lytic activity, but cold target competition studies indicated that all of the lysis resulted from NK activity. This was verified by using inhibition studies with the use of monoclonal antibodies. OKT 3 and anti-HLA antibodies that block CTL function caused no reduction in kill. In contrast, anti-lymphocyte function antigen-1 (anti-LFA-1), which blocks both NK and CTL function, significantly inhibited lysis. These results serve as a functional confirmation of earlier findings of a very weak expression of HLA-A,B,C and beta 2-microglobulin on neuroblastoma cells.
人类神经母细胞瘤细胞对直接细胞毒性的敏感性此前尚未确定。鉴于其侵袭性生长和低HLA表达，这一点尤其令人关注。在4小时的细胞介导的淋巴细胞溶解（CML）试验中，发现神经母细胞瘤细胞系CHP 100和CHP 126是理想的靶细胞。来自新鲜外周血淋巴细胞（PBL）和NK克隆3.3的自然杀伤（NK）细胞对这两种细胞系均具有高裂解活性。我们还研究了混合淋巴细胞培养产生的细胞毒性细胞系，其中含有针对神经母细胞瘤靶细胞系上存在的HLA抗原的同种特异性细胞毒性T淋巴细胞（CTL）。这些细胞系确实表现出优异的裂解活性，但冷靶竞争研究表明，所有的裂解均源于NK活性。通过使用单克隆抗体进行抑制研究对此进行了验证。阻断CTL功能的OKT 3和抗HLA抗体并未导致杀伤作用降低。相反，阻断NK和CTL功能的抗淋巴细胞功能抗原-1（抗LFA-1）显著抑制了裂解。这些结果从功能上证实了早期关于神经母细胞瘤细胞上HLA-A、B、C和β2-微球蛋白表达非常弱的发现。
