Immune environment effects on naive T cells

免疫环境对初始 T 细胞的影响

• 批准号: 7055290
• 负责人: MARY F PREMENKO-LANIER
• 金额: $ 4.07万
• 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 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055290
• 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）：本研究的目的是研究持续的急性和慢性感染以及暴露于肿瘤如何影响幼稚的旁观者T细胞群。据推测，在T细胞受体特异性激活之前，幼稚T细胞暴露的环境会影响其对抗原的反应能力。具体目的是分析急性和慢性感染期间初始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初始T细胞产生免疫反应的能力。此外，确定在慢性感染或肿瘤模型中引入治疗性细胞因子对旁观者幼稚T细胞的影响。利用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肺癌肿瘤移植模型中。然后将恢复的卵母细胞过继地转移到正常的LCMV免疫受体中，以确定其对卵母细胞感染的反应能力。这项研究将为治疗的发展和时机提供线索，并将导致慢性疾病和免疫抑制期间靶向幼稚T细胞活力的治疗发展。