系统免疫学分析CXCR5+滤泡T细胞在调控抗体免疫衰老及提高老年疫苗效力中的机制

人口老龄化带来的健康问题日益严重，衰老带来的免疫系统异常是老年人同成年人相比病毒感染后较高重症和死亡风险的原因之一，也是老年人流感疫苗等多种疫苗接种效力较低的因素之一，但其中的抗体免疫调控过程和机制尚未不清晰。CXCR5+滤泡辅助Tfh, 调节Tfr和杀伤Tfc细胞是近年来新发现的参与生发中心高质量抗体生成的重要调控细胞。前期研究发现，健康和平衡的Tfh细胞对促进病毒和疫苗过程中的高效抗体生成和免疫稳态有重要作用，而Tfr和Tfc细胞可起到负调控作用。同时老年人外周血Tfh细胞随年龄下降，而Tfr和Tfc细胞随年龄升高。本课题在已有基础上，利用系统免疫学分析方法和小鼠模型，对滤泡T细胞调控衰老后高质量抗体生成中的免疫学作用和机制展开研究，探讨通过衰老中滤泡T细胞的免疫再平衡来有效提高老年人的抗病毒抗体生成和疫苗效力，填补衰老免疫学研究空白，为开发针对老年人的精准靶向个体化疫苗奠定基础。

Increased aging population associates with significantly increased healthy burden and cost in the society. The abnormal immune system caused by aging is one of the reasons for the higher risk of severe illness and mortality in the elderly compared with adults during viral infection. It is also one of the causes of poor vaccine efficacy and reduced protection occurred in the elderly. However, the mechanism of how aging affects the antibody-mediated immune response is not yet clear. CXCR5+ follicular helper (Tfh), regulatory (Tfr) and cytotoxic (Tfc) T cells are newly discovered follicular cells that are pivotal in regulating high-affinity and long-lived antibody response in the germinal center. Previous studies have found that healthy and balanced Tfh cells are critical to positively regulate such high-quality antibody production during viral infection and vaccination, while Tfr and Tfc cells can play a negative role. Our previous study found that the frequency of peripheral CXCR5+ follicular Tfh cells the elderly decreased with age, while Tfr and Tfc cells positively associated with age. Correspondingly, a similar imbalance of follicular T cells populations was found in the aged mice. In this project, we will apply the emerging systems immunology analysis methods and novel mouse models to study the mechanisms of CXCR5+ follicular T cells in regulating the high-quality antibody production in aging population and explore whether reinstate the immune balance of CXCR5+ follicular T cell population can effectively improve the effectiveness of antiviral antibody production and vaccination efficacy in the elderly. This project will fill the research gap in the field of aging immunology and lay the foundation for the future development of novel personalized and precise vaccines for the elderly.