T LYMPHOCYTE, T CELL RECEPTOR, CELLULAR IMMUNITY, IMMUNOTHERAPY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是研究正在进行的急性和慢性感染和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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.