論文 - 詳細
| RRC ID | 41509 |
|---|---|
| 著者 | Hagihara M, Gansuvd B, Ueda Y, Tsuchiya T, Masui A, Tazume K, Inoue H, Kato S, Hotta T. |
| タイトル | 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. |
| ジャーナル | Cancer Immunol Immunother |
| Abstract |
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:TCRValpha24(+) Vbeta11(+) UCB- or PB-NKT cells were isolated by sorting and activated by alpha-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 by (51)Cr-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. |
| 巻・号 | 51(1) |
| ページ | 1-8 |
| 公開日 | 2002-3-1 |
| DOI | 10.1007/s00262-001-0246-2 |
| PMID | 11845254 |
| MeSH | Antigens, CD1 / analysis Antigens, CD1 / immunology Antigens, CD1d Antigens, Neoplasm / analysis Antigens, Neoplasm / immunology Autoimmunity Blood Cells Cell Line, Transformed Cell Separation Cytotoxicity, Immunologic / drug effects Dendritic Cells / immunology Dose-Response Relationship, Drug Fetal Blood / cytology* Fetal Blood / immunology Flow Cytometry Galactosylceramides / immunology Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor Hematologic Neoplasms / immunology Hematologic Neoplasms / pathology Humans Interleukin-12 / pharmacology Interleukin-18 / pharmacology Killer Cells, Natural / drug effects Killer Cells, Natural / immunology* Lymphocyte Activation / drug effects Muromonab-CD3 / pharmacology* Neoplastic Stem Cells Receptors, Antigen, T-Cell, alpha-beta / genetics* T-Lymphocyte Subsets / drug effects T-Lymphocyte Subsets / immunology* Tumor Cells, Cultured |
| IF | 5.442 |
| 引用数 | 20 |
| WOS 分野 | IMMUNOLOGY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HL60(RCB0041) K562(RCB0027) MOLT-4(RCB0206) Jurkat(RCB0806) DAUDI(RCB1640) RAJI(RCB1647) U-937 DE-4(RCB0435) |