TC1 AND TC2 ACTIVITY IN MALIGNANCY

恶性肿瘤中的 TC1 和 TC2 活性

• 批准号: 2895662
• 负责人: Patrick Michael Flood
• 金额: $ 20.34万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-20 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2895662
• 关键词: CD antigens; MHC class I antigen; cellular immunity; cytokine; cytotoxic T lymphocyte; helper T lymphocyte; laboratory mouse; neoplasm /cancer immunology; tissue /cell culture

DESCRIPTION (Adapted from the Applicant's Abstract): CD8 T-cells are a major immunologic effector cell mediating resistance to cancer. Recently it has been found that CD8+ T-cells like CD4+ T-cells can be divided into two distinct subsets. By similarities with Th1 and Th2 subsets of CD4, the CD8+ T-cell subsets have been designated as Tc1 and Tc2. This division was made on the basis of the cytokines they produce. These subsets have been defined in vitro only and nothing has so far been shown regarding their distribution or function in vivo. The goal of the project proposed in this new application is to establish the existence of these subsets in vivo, to characterize their activation and functional requirements, and to determine their role in the protective immunity against transplanted malignant cells. A highly immunogenic UV-induced mouse tumor cell line has been selected as a model. Decrease in resistance to this immunogenic tumor can be observed in animals acutely treated with UV light or in advanced age. This decrease in resistance coincides with a decline in the CD8+ T-cell-mediated protective mechanisms as well as a change in cytokine production by CD8+ T-cells in response to antigenic challenge. The Tc1 response characterized by CD8+ T-cells which produce IL-2 and IFNg changes over time to a Tc2 response characterized by production of IL-4 and IL-10. This application will investigate the cause for such change, the role that the tumor may play, and whether preferential activation of Tc1 versus Tc2 in vivo correlates with protective or susceptible immunity to this tumor line.

描述(改编自申请者摘要)：CD8 T细胞是一种 介导抗癌的主要免疫效应细胞。最近它 已发现CD8+T细胞和CD4+T细胞一样可以分为两类 不同的子集。通过与CD4的Th1和Th2亚群的相似性，CD8+ T细胞亚群被指定为Tc1和Tc2。这一划分是 根据它们产生的细胞因子。已经定义了这些子集 只是在体外，到目前为止还没有关于它们的分布的任何信息 或在体内发挥作用。在这个新项目中提出的项目目标 应用是确定这些子集在体内的存在，以 确定它们的激活和功能要求，并确定 它们在对移植的恶性细胞的保护性免疫中的作用。 一种高免疫原性的紫外线诱导的小鼠肿瘤细胞系被选为 模特。对这种免疫原性肿瘤的耐药性下降可以观察到 用紫外光或高龄动物进行尖锐治疗的动物。这一下降在 耐药性与CD8+T细胞介导的保护性下降不谋而合 CD8+T细胞产生细胞因子的机制及变化 对抗原挑战的反应。以CD8+为特征的Tc1应答 产生IL-2和IFNG的T细胞随着时间的推移而变化为Tc2应答 以产生IL-4和IL-10为特征。此应用程序将 调查这种变化的原因，肿瘤可能发挥的作用，以及 Tc1相对于Tc2在体内的优先激活是否与 对这种肿瘤的保护性或易感性免疫。