論文 - 詳細
| RRC ID | 65849 |
|---|---|
| 著者 | Domae E, Hirai Y, Ikeo T, Goda S, Shimizu Y. |
| タイトル | Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells. |
| ジャーナル | Oncotarget |
| Abstract |
Vγ9Vδ2 T cells, the major subset of the human peripheral blood γδ T-cell, respond to microbial infection and stressed cells through the recognition of phosphoantigens. In contrast to the growing knowledge of antigen-mediated activation mechanisms, the antigen-independent and cytokine-mediated activation mechanisms of Vγ9Vδ2 T cells are poorly understood. Here, we show that interleukin (IL) -12 and IL-18 synergize to activate human ex vivo-expanded Vγ9Vδ2 T cells. Vγ9Vδ2 T cells treated with IL-12 and IL-18 enhanced effector functions, including the expression of IFN-γ and granzyme B, and cytotoxicity. These enhanced effector responses following IL-12 and IL-18 treatment were associated with homotypic aggregation, enhanced expression of ICAM-1 and decreased expression of the B- and T-lymphocyte attenuator (BTLA), a co-inhibitory receptor. IL-12 and IL-18 also induced the antigen-independent proliferation of Vγ9Vδ2 T cells. Increased expression of IκBζ, IL-12Rβ2 and IL-18Rα following IL-12 and IL-18 stimulation resulted in sustained activation of STAT4 and NF-κB. The enhanced production of IFN-γ and cytotoxic activity are critical for cancer immunotherapy using Vγ9Vδ2 T cells. Thus, the combined treatment of ex vivo-expanded Vγ9Vδ2 T cells with IL-12 and IL-18 may serve as a new strategy for the therapeutic activation of these cells. |
| 巻・号 | 8(28) |
| ページ | 45928-45942 |
| 公開日 | 2017-7-11 |
| DOI | 10.18632/oncotarget.17498 |
| PII | 17498 |
| PMID | 28521284 |
| PMC | PMC5542238 |
| MeSH | Adaptor Proteins, Signal Transducing Cell Proliferation / drug effects Cells, Cultured Cytokines / metabolism* Humans I-kappa B Proteins / genetics Lymphocyte Activation / drug effects* Lymphocyte Activation / immunology* Nuclear Proteins / genetics Receptors, Antigen, T-Cell, gamma-delta / metabolism* T-Lymphocyte Subsets / drug effects* T-Lymphocyte Subsets / physiology* |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RPMI8226(RCB3010) MG-63(RCB1890) |