Dendritic cell maturation by CD11c- T cells and Vα24+ natural killer T-cell activation by α-galactosylceramide
Dendritic cell maturation by CD11c- T cells and Vα24+ natural killer T-cell activation by α-galactosylceramide
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DOI：
10.1002/ijc.21197
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发表时间：
2005-11-01
影响因子：
6.4
通讯作者：
Nakayama, T
中科院分区：
文献类型：
--
作者：
Ishikawa, E;Motohashi, S;Nakayama, T
人类恒定 V α 24(+) 自然杀伤 T (NKT) 细胞在受到刺激后表现出有效的抗肿瘤活性。激活内源性 V α 24(+) NKT 细胞将是治疗癌症患者的一种策略。例如，负载有糖脂 NKT 细胞配体 α-半乳糖苷神经酰胺（α GalCer，KRN7000）的树突状细胞 (DC) 是体内激活和扩增功能性 V α 24(+) NKT 细胞的可能工具。在本报告中，我们证明，用IL-2和GM-CSF培养的加载αGalCer的全PBMC（IL-2/GM-CSF培养的PBMC）诱导的V alpha 24（+）NKT细胞的扩增水平和产生IFN-γ的能力优于用IL-2和GM-CSF培养的单核细胞来源的CD11c（+）DC（moDC）诱导的细胞。 IL-4 和 GM-CSF。有趣的是，IL-2/GM-CSF培养的PBMC中的CD11c(+)细胞在没有进一步刺激的情况下表现出成熟的表型，并对V α 24(+) NKT细胞发挥有效的刺激活性，使其能够优先产生IFN-γ，其程度相当于用LPS或细胞因子混合物刺激诱导的成熟moDC。在IL-2/GM-CSF培养的PBMC中与CD11c(-)细胞共培养可诱导moDC的成熟。特别是，CD11c(-)CD3(+) T 细胞似乎在 DC 成熟中发挥重要作用。此外，TNF-α优先由IL-2/GM-CSF培养的PBMC中的CD11c(-)CD3(+) T细胞产生，并参与moDC的成熟。因此，CD11c(-) T 细胞通过 TNF-α 产生诱导 DC 成熟，似乎导致 V α 24(+) NKT 细胞有效扩增和激活，优先产生 IFN-γ。 (c) 2005 年 Wiley-Liss, Inc.
Human invariant V alpha 24(+) natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous V alpha 24(+) NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, alpha-galactosylceramide (alpha GalCer, KRN7000), are a possible tool for the activation and expansion of functional V alpha 24(+) NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN-gamma of V alpha 24(+) NKT cells induced by alpha GalCer-loaded whole PBMCs cultured with IL-2 and GM-CSF (IL-2/GM-CSF-cultured PBMCs) were superior to those of cells induced by monocyte-derived CD11c(+) DCs (moDCs) developed with IL-4 and GM-CSF. Interestingly, CD11c(+) cells in the IL-2/GM-CSF-cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on V alpha 24(+) NKT cells to enable them to produce IFN-gamma preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c(-) cells in the IL-2/GM-CSF-cultured PBMCs induced maturation of moDCs. In particular, CD11c(-)CD3(+) T cells appeared to play important roles in DC maturation. In addition, TNF-alpha was preferentially produced by CD11c(-)CD3(+) T cells in IL-2/GM-CSF-cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c(-) T cells through TNF-alpha production appears to result in the efficient expansion and activation of V alpha 24(+) NKT cells to produce IFN-gamma preferentially. (c) 2005 Wiley-Liss, Inc.