TC1 AND TC2 ACTIVITY IN MALIGNANCY

恶性肿瘤中的 TC1 和 TC2 活性

• 批准号: 2458277
• 负责人: Patrick Michael Flood
• 金额: $ 18.81万
• 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 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458277
• 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（改编自申请人的摘要）：CD 8 T细胞是一种免疫调节剂。 主要的免疫效应细胞介导对癌症的抗性。 最近它 已经发现，CD 8 + T细胞像CD 4 + T细胞一样可以分为两种， 不同的子集 由于与CD 4的Th 1和Th 2亚群相似，CD 8 + T细胞亚群也与Th 1和Th 2亚群相似。 T细胞亚群被命名为Tc 1和Tc 2。 这种划分是由 基于它们产生的细胞因子。 这些子集已定义 仅在体外，迄今为止尚未显示其分布 或在体内起作用。 在这个新的项目中提出的目标 应用是在体内建立这些亚群的存在， 描述其激活和功能要求，并确定 它们在针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已被选为 模型 可以观察到对这种免疫原性肿瘤的抗性降低， 用紫外线进行急性治疗或处于高龄的动物。 的这种降低 耐药性与CD 8 + T细胞介导的保护性T细胞功能的下降相一致。 机制以及CD 8 + T细胞产生细胞因子的变化， 对抗原攻击的反应。 以CD 8+为特征的Tc 1应答 产生IL-2和IFNg的T细胞随时间变化为Tc 2应答 其特征在于产生IL-4和IL-10。 此应用程序将 调查这种变化的原因，肿瘤可能发挥的作用， 体内Tc 1相对于Tc 2的优先活化是否与 保护性或易感性免疫。