Immune environment effects on naive T cells

描述（由申请人提供）：本研究的目的是检查正在进行的急性和慢性感染以及暴露于肿瘤如何影响幼稚旁观者T细胞群。假设初始T细胞在T细胞受体特异性活化之前所暴露的环境将影响其对抗原应答的能力。具体目的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慢性抗原暴露如何影响旁观者幼稚T细胞产生免疫应答的能力。此外，为了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幼稚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感染或刘易斯肺癌肿瘤移植模型。然后，将经传代的OVA幼稚细胞过继转移到正常的LCMV免疫受体中，以确定它们对OVA感染的应答能力。这项研究将为治疗的发展和时机提供线索，并将导致针对慢性疾病和免疫抑制期间幼稚T细胞活力的治疗发展。

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.