NKG2D公司
化学
白细胞介素2受体
外周血单个核细胞
CD44细胞
癌症研究
细胞毒性T细胞
白细胞介素21
穿孔素
分子生物学
免疫学
体外
生物
生物化学
作者
Wen Li,Shuji Kubo,A Okuda,Hideyuki Yamamoto,Haruyasu Ueda,Toshiyuki Tanaka,Hideji Nakamura,Hiromichi Yamanishi,Nobuyuki Terada,Haruki Okamura
出处
期刊:Journal of Immunotherapy
[Ovid Technologies (Wolters Kluwer)]
日期:2010-04-01
卷期号:33 (3): 287-296
被引量:55
标识
DOI:10.1097/cji.0b013e3181c80ffa
摘要
Zoledronate (Zol) has recently been shown to expand gammadelta T cells that play important roles in host defenses against infection and tumors. In this study, we examined effects of interleukin-18 (IL-18) on expansion of gammadelta T cells in human peripheral blood mononuclear cells (PBMCs) stimulated by Zol and IL-2. The expansion of gammadelta T cells stimulated by Zol and IL-2 was strongly promoted by exogenous IL-18, and to the contrary, inhibited by neutralizing anti-IL-18 receptor antibody. The gammadelta T cells that expanded in the presence of Zol, IL-2, and IL-18 exhibited the phenotype of effector memory cells characterized by CD44 (+), CD27 (-), and CD45RA (-). In addition, they expressed NKG2D, perforin, CD94, CD25, and CD122, and 15% to 40% of them were positive for CD56. Incubation of gammadelta T cells in the presence with IL-18 produced GM-CSF, IFN-gamma, and TNF-alpha at much higher levels than those incubated without IL-18. They showed strong cytotoxicity against tumor cells including mesothelioma cells and inhibited growth of xenograft of mesothelioma in mice. These observations indicate that IL-18 can efficiently promote expansion of gammadelta T cells with potent antitumor activity.
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