Development of New Immunotherapy for Oral Cancer Using Dendritic Cells

利用树突状细胞开发新的口腔癌免疫疗法

• 批准号: 13470443
• 负责人: MATSUMOTO Goichi
• 金额: $ 6.08万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470443/
• 关键词: LFA-1; NKT; costimulation; α-GalCer; DC; DC; CD28; 樹状細胞; NKT細胞

Natural killer T (NKT) cells produce large amounts of cytokines associated with both the Th1 response (IFN-γ) and Th2 response (IL-4) after being stimulated by the synthetic CD1d ligand α-galactosylceramide (α-GalCer) by their invariant Vα14 receptor. However, the role played by adhesion or co-stimulation molecules in the activation of NKT cells by α-GalCer remains unclear. To address this issue, LFA-1^+ and CD28^+ mice were used to investigate IL-4 and IFN-γ production by NKT cells following α-GalCer stimulation. LFA-1^+ mice showed increased IL-4 production in response to in vitro and in vivo polarized Th2-type responses, represented by activation of B cells and serum IgE elevation. In contrast, impairment of production of IL-4 and IFN-γ in CD28^+ mice resulted in a profound inability to polarize the Th2-type response, represented by the abolishment of serum IgE. These results imply that the LFA-1 adhesion receptor and the CD28 co-stimulatory receptor selectively regulate Th1- and Th2-like functions of α-GalCer-activated NKT cells.

自然杀伤 T (NKT) 细胞在受到合成 CD1d 配体 α-半乳糖神经酰胺 (α-GalCer) 刺激后，通过其不变性产生大量与 Th1 反应 (IFN-γ) 和 Th2 反应 (IL-4) 相关的细胞因子Vα14 受体。然而，粘附或共刺激分子在 α-GalCer 激活 NKT 细胞中所起的作用仍不清楚。为了解决这个问题，LFA-1^+。 CD28^+ 小鼠用于研究 α-GalCer 刺激后 NKT 细胞产生的 IL-4 和 IFN-γ，LFA-1^+ 小鼠在体外和体内极化 Th2 型反应中显示出 IL-4 产量增加。相反，CD28^+小鼠中IL-4和IFN-γ的产生受损导致严重无法极化Th2型反应，以B细胞激活和血清IgE升高为代表。血清 IgE 的消除这些结果表明 LFA-1 粘附受体和 CD28 共刺激受体选择性调节 α-GalCer 激活的 NKT 细胞的 Th1 和 Th2 样功能。