Killing activity of human umbilical cord blood-derived TCRValpha24+ NKT cells against normal and malignant hematological cells in vitro: a comparative study with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT cells
Killing activity of human umbilical cord blood-derived TCRValpha24+ NKT cells against normal and malignant hematological cells in vitro: a comparative study with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT cells
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DOI：
10.1007/s00262-001-0246-2
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发表时间：
2002-03
期刊：
影响因子：
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通讯作者：
M. Hagihara;B. Gansuvd;Y. Ueda;T. Tsuchiya;Aya Masui;K. Tazume;H. Inoue;S. Kato;T. Hotta
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文献类型：
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作者：
M. Hagihara;B. Gansuvd;Y. Ueda;T. Tsuchiya;Aya Masui;K. Tazume;H. Inoue;S. Kato;T. Hotta
目的：探讨人脐带血（UCB）源性自然杀伤T（NKT）细胞作为免疫效应细胞对血液系统恶性肿瘤的杀伤作用，以及自体、异体树突状细胞（DCs）和EB转化细胞系（EBCL）的作用。通过干细胞因子加IL-15从⑶ 34+细胞诱导UCB-NK细胞。UCB-T细胞主要被抗CD 3单克隆抗体激活。用IL-2（100 U/ml）培养细胞，用51 Cr释放法测定细胞毒活性。结果：UCB-NKT细胞对多种恶性血液病的杀伤活性与UCB-NK细胞相似，但不能杀伤NK细胞敏感的靶细胞K562。活性水平与PB-NKT细胞的活性水平非常相似。相比之下，与UCB-NK或NKT细胞相比，OKT-3激活的UCB-T淋巴细胞显示出更强、更广泛的杀伤范围。IL-12、IL-18或更高剂量的IL-2上调活性;然而，包括新鲜白血病细胞在内的几个靶点仍然具有抗性。NKT细胞以与T细胞相似的水平杀死自体或同种异体DC，但不能杀死被T细胞有效杀死的同种异体EBCL。而NK细胞对DC或EBCLs仅表现出边缘或无杀伤作用。讨论：人NKT细胞的抗癌活性取决于Th 1-细胞因子的浓度或组合。基本上，这些细胞可能不会有助于血液恶性肿瘤的免疫监视，如对恶性细胞的相对低的细胞毒性以及对自身DC的相当强的杀伤所示。
Purpose:We aimed to determine the effects of human umbilical cord blood (UCB)-derived natural killer T (NKT) cells as immunological effectors against hematological malignancies, as well as auto- or allo-dendritic cells (DCs) or EB transformed cell lines (EBCLs).Materials:TCRVα24+Vβ11+UCB- or PB-NKT cells were isolated by sorting and activated by α-galactosylceramide-pulsed autologous DCs. UCB-NK cells were induced from CD34+cells by stem cell factor plus IL-15. UCB-T cells were primarily activated by anti-CD3 monoclonal antibody. All those effectors were cultured with IL-2 (100 U/ml), and their cytotoxic activities were evaluated by51Cr-release assay. UCB-NKT cells were cultured with IL-12, IL-18 or higher dose of IL-2 (1000 U/ml), and again tested for the cytotoxicity against selected targets.Results:UCB-NKT cells exhibited a pattern of killing activity against various hematological malignancies similar to that of UCB-NK cells, but could not kill K562, which was a vulnerable target for NK cells. The level of activity was quite similar to that of PB-NKT cells. In contrast, OKT-3-activated UCB-T lymphocytes showed a stronger and wider spectrum of killing compared with UCB-NK or NKT cells. IL-12, IL-18 or a higher dose of IL-2 upregulated the activity; however several targets, including fresh leukemic cells, still remained resistant. NKT cells killed auto- or allo-DCs at a level similar to that of T cells, but could not kill allo-EBCLs, which were efficiently killed by T cells. While NK cells showed only marginal or no killing against DC or EBCLs.Discussion:The anti-cancer activity of human NKT cells depends on the concentrations or the combination of Th1-cytokines. Basically, those cells might not be contributing to the immune surveillance of hematological malignancies, as shown by a relatively low cytotoxicity against malignant cells, together with the quite strong killing against auto-DCs.