Departmental Bulletin Paper ゾレドロン酸で前処置した白血病性形質細胞様樹状細胞株PMDC11を用いたγδT細胞の効果的な誘導
Efficient amplification of γδT cell by PMDC11 cells treated with zoledoronic acid

西澤, 幹則  ,  成田, 美和子  ,  岩谷, 俊平  ,  大岩, 恵理  ,  内山, 孝由  ,  高橋, 益廣  ,  Nishizawa, Yoshinori  ,  Narita, Miwako  ,  Uchiyama, Takayoshi  ,  Iwaya, Shunpei  ,  Oiwa, Eri  ,  Takahashi, Masuhiro

12 ( 1 )  , pp.69 - 75 , 2015-09 , 新潟大学医学部保健学科
γδT細胞は様々な腫瘍細胞に対する抗腫瘍活性を有しており, in vitroにおいてゾレドロン酸を用いる事で末梢血単核球(PBMNC)から選択的に誘導することが可能であることから, γδT細胞の腫瘍に対する養子免疫療法への応用が期待されている。また, ゾレドロン酸で前処置した単球由来樹状細胞(moDC)でPBMNCを刺激することで, 従来の培養法に比べ効果的にγδT細胞を誘導すること可能であるという報告がある。そこで本検討では, 当研究室で樹立した白血病性形質細胞様樹状細胞株PMDC11を用いた場合でも, moDCと同様にγδT細胞をより効果的に誘導出来るか否かを検討した。ゾレドロン酸で24時間前処置したPMDC11でPBMNCを刺激することで従来の培養法に比べより効果的にγδT細胞を誘導することが可能であった。また,誘導されたγδT細胞の腫瘍細胞株に対する細胞傷害活性も確認された。以上のことから, γδT細胞を用いた養子免疫療法へのPMDC11の応用の可能性が示唆された。
γδT cells possess a cytotoxic activity against various human tumor cells and can be easily expanded by phosphoantigen stimulation in vitro. Thus, adoptive immunotherapy with γδT cells is an attractive strategy for tumor. It has been reported that dendritic cells (DCs) treated with aminobisphosphonates, such as zoledoronic acid (ZA), could more efficiently expand γδT cells than conventional culture protocol without DCs in tumor patients. On the other hand, we have reported that a leukemic plasmacytoid dendritic cell line transduced with CD80 gene, PMDC11, which was previously established in our laboratory, possess the function equivalent to conventional DCs. Here, in order to establish the method of generating potent γδT cells, we investigated whether ZA-treated PMDC11 cells could also expand γδT cells efficiently. γδT cell expansions were performed by co-culturing PB mononuclear cells (MNCs) with PMDC11 cells incubated with ZA for 24 hours. Co-culturing of PBMNCs with ZA-treated PMDC11 cells induced efficient expansion of γδT cells compared with the conventional culture protocol without PMDC11 cells. In the cytotoxicity assay, expanded γδT cells were used as effector cells and myeloma cell line (RPMI8226) was used as target cells. This assay demonstrated that expanded γδT cells possessed cytotoxicity against RPMI8226 in an effector-to-target ratiodependent manner. These finding showed that ZA-treated PMDC11 cells efficiently expanded γδT cells with cytotoxic activity. The present date suggested that the method of generating γδT cells by co-culturing PBMNCs with ZA-treated PMDC11 cells could be applicable to an efficient γδT cell adoptive immunotherapy for tumors.

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