Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of γδ T cells expanded from peripheral blood cells by stimulation with zoledronate
Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of γδ T cells expanded from peripheral blood cells by stimulation with zoledronate
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DOI：
10.1080/14653240600620200
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发表时间：
2006-05-01
期刊：
影响因子：
4.5
通讯作者：
Takahashi, M
中科院分区：
文献类型：
--
作者：
Watanabe, N;Narita, M;Takahashi, M
为了建立有效的基于γ δ T细胞的肿瘤免疫治疗，我们探索了一种通过用I型IFN刺激gd T细胞来增强gd T细胞对白血病细胞的细胞毒性的方法。为了活化gd T细胞，将gd T细胞与I型IFN（HLBI、IFN-α 2b和IFN-β）一起培养1-3天。结果用抗γ δ TCR单克隆抗体磁珠法扩增并纯化的gd T细胞对淋巴系和髓系白血病细胞株及新鲜髓系白血病细胞均具有细胞毒活性。通过用I型IFN培养扩增的γ δ T细胞，活化标志物CD 69的表达增加，并且细胞计数珠阵列显示gd T细胞产生的IFN-γ升高。另外，用HLBI培养的gd T细胞对白血病细胞的细胞毒作用明显增强。讨论本研究证实I型IFN能增强扩增的gd T细胞的抗白血病细胞毒作用，这意味着体外双膦酸盐（如唑来膦酸盐）-扩大和I型IFN-γ活化的gd T细胞可用于血液恶性肿瘤如白血病和淋巴瘤的免疫治疗。
Background In order to establish efficient gamma delta T-cell based tumor immunotherapy, we explored a method to enhance the cytotoxicity of gd T cells against leukemia cells by stimulating gd T cells with type I IFN.Methods gd T cells were expanded from normal PBMC by culturing with zoledronate and a low concentration of IL-2 for 2 weeks. For the activation of gd T cells, gd T cells were cultured with type I IFN (HLBI, IFN-alpha 2b and IFN-beta) for 1-3 days. The cytotoxicity of HLBI-activated gd T cells against leukemia cell lines and fresh leukemia cells was evaluated by Cr-51-release assay.Results gd T cells, which were expanded and purified with magnetic beads using an anti-gamma delta TCR MAb, were demonstrated to be cytotoxic against leukemia cell lines of both lymphoid and myeloid origin and fresh myeloid leukemia cells. By culturing expanded gamma delta T cells with type I IFN, the expression of the activation marker CD69 was increased and the cytometric bead array showed an elevated production of IFN-gamma by gd T cells. In addition, the cytotoxicity of gd T cells against leukemia cells was definitely enhanced by culturing gd T cells with HLBI.Discussion The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gd T cells, which implies that in vitro bisphosphonate ( such as zoledronate)-expanded and type I IFN-activated gd T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma.