Departmental Bulletin Paper OK432及びIFN-γ刺激による白血病性形質細胞様樹状細胞株(PMDC05)の直接細胞傷害活性の検出
Direct cytotoxicity of leukemic plasmacytoid dendritic cell line(PMDC05) stimulated with OK432 and IFN-γ.

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

12 ( 1 )  , pp.77 - 82 , 2015-09 , 新潟大学医学部保健学科
抗原ペプチドが同定されていない腫瘍に対する細胞傷害性T細胞(CTL)を誘導するために,当研究室で樹立した白血病性形質細胞様樹状細胞株(leukemic plasmacytoid dendritic cell line; PMDC05)の直接的な細胞傷害活性を検出することを目的とした。ペニシリン凍結乾燥処理したStreptococcus pyogenesの菌体成分(OK432)及びIFN-γを用いてPMDC05の刺激培養を行った。OK432及びIFN-γで刺激されたPMDC05は,刺激なしに比べてサイトカイン産生が増強し,標的細胞を有意に傷害した。以上のことから,OK432及びIFN-γで刺激されたPMDC05は,腫瘍細胞との共培養によって腫瘍抗原を提示し,腫瘍抗原特異的CTLを誘導するための有力な抗原提示細胞になり得ると考えられた。
A leukemic plasmacytoid dendritic cell line, PMDC05, which was previously established in our laboratory, showed the ability of inducing antigen specific cytotoxic T lymphocytes. For tumors that antigenic peptides are not identified, it would be necessary for PMDC05 to have direct cytotoxicity against tumor cells to uptake tumor antigens for presenting them to T cells. Therefore, we aimed to investigate the effects of OK432, penicillin-inactivated and lyophilized preparation of Streptococcus pyogenes which has been clinically used in Japan for more than 30 years, to activate PMDC05 cells. Stimulation of PMDC05 cells with OK432 and IFN-γenhanced the expression of CCR7 and TNF-related apoptosisinducing ligand (TRAIL). Also, we detected a higher cytokine production such as IL-6 and TNF-α compared with unstimulated PMDC05 cells. Furthermore, PMDC05 cells stimulated with OK432 and IFN-γshowed direct cytotoxicity against the tumor cell targets (T2A24 cells) expressing death-inducing receptors (DR4 and DR5). This might have occurred due to binding of TRAIL expressed on PMDC 05 cells with DR4/5 on T2A24 cells. These data suggest that by stimulation with OK432 and IFN-γPMDC05 cells could acquire direct antitumor cytotoxicity, which may be beneficial for PMDC05 cells to uptake tumor cell components for antigen presentation in case of PMDC05 cells are co-cultured with tumor cells. OK432/IFN-γ-stimulated PMDC05 cells, which are loaded with tumor antigen by co-culturing with tumor cells, could be used as potent antigen presenting cells for generating antigen specific cytotoxic T lymphocytes (CTLs) in antitumor cellular immunotherapy.

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