T细胞免疫组库与高原红细胞增多症易感性的关系及机制研究

本课题组前期研究发现CD4+T淋巴细胞特定亚群及其分泌的细胞因子参与了高原红细胞增多（症）过程，由于高红症存在个体易感倾向，而个体由于自身MHC、感染、环境等因素造成的T细胞多样性特征被认为与T细胞的极化及生成细胞因子的类型与水平有关，因此我们推测个体T细胞组库可能与高红症的发病存在一定关系。本项目拟以高红症患者及高原健康人群外周血T淋巴细胞为研究对象，综合应用TCR基因谱系扫描分析和TCR免疫组库高通量测序技术，深入研究TCR组库特征与CD4+T细胞亚群谱、造血因子谱及高红症易感性的关联性，并寻找高红症患者典型性的T细胞克隆和TCR共性结构特征。在此基础上，探索低氧环境下特殊T细胞克隆影响红系造血的相关机制，并通过生物信息学手段初步探索与HAPC特定TCR相关的遗传因素和环境抗原因素，本课题研究结果有望为高红症的防治和易感者的筛选提供新的思路和干预靶点。

We previously observed that T lymphocytes and secreting cytokines were related to erythropoiesis during hypoxia and pathogenesis of high altitude polycythemia (HAPC). Due to a relationship between T-cell repertoire diversity and T-subset polarization as well as different cytokines production, we presume that T-cell receptor (TCR) repertoire specificity caused by self MHC, infection and environmental factor seems to play important role in individual susceptibility of HAPC. In this study, the expressions of TCR genes for HAPC patients and healthy high-altitude migrators were evaluated by gene scanning and high-throughput sequencing technique. Meanwhile, the correlations among TCR repertoire, T subsets, produced erythroid cytokines and susceptibility of HAPC were analyzed. The dominant T-cell clones and representative TCR structures of HAPC patients were also discovered. Then, we will explore why T-cell clones with special TCR could influence growth of erythroid cells under hypoxia and cause severity of HAPC. Meanwhile, the genetic and environmental factors related to TCR dominance of HAPC patients were also analyzed by method of bioinformatics. This study may provide a new idea for prevention, treatment and of HAPC as well as screening of susceptible persons.