英国巴伯拉罕研究所Michelle A. Linterman团队近期取得重要工作进展。他们研究发现T滤泡辅助细胞的空间失调会损害衰老过程中的疫苗反应。相关研究成果2023年5月22日在线发表于《自然—免疫学》杂志上。

据介绍，生发中心（GC）反应的程度和质量随着年龄的增长而下降，导致老年人疫苗诱导的免疫力低下。功能性GC需要多种细胞类型在时间和空间上的协调，特别是在其两个功能不同的隔间：亮区和暗区。在老年小鼠中，存在CXCR4介导的T滤泡辅助细胞（T_FH）在暗区的定位错误，以及在亮区的滤泡树突细胞（FDC）的压缩网络。

研究人员表明，T_FH细胞定位对于抗体反应的质量和免疫后FDC网络的扩展至关重要。老年小鼠中较小的GC和压缩的FDC网络通过使用CXCR5提供与FDC共定位的T_FH细胞来校正。这表明GC反应中的年龄依赖性缺陷是可逆的，并表明T_FH细胞支持基质细胞对疫苗的反应。

附：英文原文

Title: Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging

Author: Silva-Cayetano, Alyssa, Fra-Bido, Sigrid, Robert, Philippe A., Innocentin, Silvia, Burton, Alice R., Watson, Emily M., Lee, Jia Le, Webb, Louise M. C., Foster, William S., McKenzie, Ross C. J., Bignon, Alexandre, Vanderleyden, Ine, Alterauge, Dominik, Lemos, Julia P., Carr, Edward J., Hill, Danika L., Cinti, Isabella, Balabanian, Karl, Baumjohann, Dirk, Espeli, Marion, Meyer-Hermann, Michael, Denton, Alice E., Linterman, Michelle A.

Issue&Volume: 2023-05-22

Abstract: The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines.

DOI: 10.1038/s41590-023-01519-9

Source: https://www.nature.com/articles/s41590-023-01519-9