期刊
JOURNAL OF IMMUNOTHERAPY
卷 33, 期 3, 页码 287-296出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e3181c80ffa
关键词
IL-18; gamma delta T-cell; cellular immunotherapy; AICD (activation-induced cell death); antiapoptotic signals
Zoledronate (Zol) has recently been shown to expand gamma delta 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 gamma delta T cells in human peripheral blood mononuclear cells (PBMCs) stimulated by Zol and IL-2. The expansion of gamma delta 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 gamma delta 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 gamma delta 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 gamma delta T cells with potent antitumor activity.
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