Immune environment effects on naive T cells

免疫环境对初始 T 细胞的影响

• 批准号: 6938857
• 负责人: MARY F PREMENKO-LANIER
• 金额: $ 4.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938857
• 关键词: T cell receptor; T lymphocyte; acute disease /disorder; antigens; cell membrane; cell population study; cellular immunity; chronic disease /disorder; cytokine; disease /disorder model; gene expression; genetically modified animals; immune response; immunotherapy; infection; laboratory mouse; leukocyte activation /transformation; microarray technology; neoplasm /cancer; neoplasm /cancer immunology; nonhuman therapy evaluation; passive immunization; postdoctoral investigator; receptor expression

DESCRIPTION (provided by applicant): The goal of this study is to examine how ongoing acute and chronic infections and exposure to tumors affect naive bystander T cell populations. It is hypothesized that the environment a naive T cell is exposed to prior to T cell receptor specific activation will affect its ability to respond to antigen. The specific aims are to analyze the status, kinetics, and stability of naive T cells during acute and chronic infections and to determine how chronic antigen exposure during persistent infections or persisting tumors has on the ability of bystander naive T cells to mount immune responses. In addition, to determine the effect of introducing therapeutic cytokines during a chronic infection or tumor model has on bystander naive T cells. Using a TCR transgenic model we will expose, by adoptive transfer, OVA TCR naive T cells to acute LCMV, chronic LCMV infection or Lewis Lung Carcinoma tumor transplant model. Recovered OVA naive cells will then be adoptively transferred into normal LCMV immune recipients to determine their ability to respond to OVA infection. This study will give clues in the development and timing of therapies and will lead to therapeutic developments for targeting naive T cell viability during chronic diseases and immune suppression.

描述（由申请人提供）：本研究的目的是检查持续的急性和慢性感染以及肿瘤暴露如何影响初始旁观者 T 细胞群。据推测，幼稚 T 细胞在 T 细胞受体特异性激活之前所接触的环境将影响其对抗原的反应能力。具体目标是分析急性和慢性感染期间幼稚 T 细胞的状态、动力学和稳定性，并确定持续感染或持续肿瘤期间的慢性抗原暴露如何影响旁观者幼稚 T 细胞发起免疫反应的能力。此外，还旨在确定在慢性感染或肿瘤模型期间引入治疗性细胞因子对旁观者初始 T 细胞的影响。使用 TCR 转基因模型，我们将通过过继转移将 OVA TCR 初始 T 细胞暴露于急性 LCMV、慢性 LCMV 感染或 Lewis 肺癌肿瘤移植模型。回收的 OVA 初始细胞将被过继转移到正常的 LCMV 免疫受体中，以确定它们对 OVA 感染做出反应的能力。这项研究将为治疗的开发和时机提供线索，并将导致针对慢性疾病和免疫抑制期间的幼稚 T 细胞活力的治疗开发。