Single cell molecular analysis of influenza vaccine responses in elderly individuals

项目摘要 我们将使用最先进的单T细胞分析技术，从分子上定义T细胞库， 65岁或以上个体的细胞免疫应答功能。背后的机制 随着年龄的增长，免疫应答下降可能是多因素的。衰老与减少 抗体分泌细胞的频率和淋巴结生发中心的数量，我们假设 这是由于CD4+ T细胞向B细胞提供足够帮助的能力受损。T滤泡辅助细胞 在生殖中心直接为B细胞提供帮助，并诱导它们成为分泌抗体的血浆 细胞我们之前已经证明了激活的外周T滤泡辅助细胞的频率 （pTfh）和循环浆母细胞接种后不久，直接相关的后续滴度 疫苗特异性抗体此外，高剂量流感疫苗（IIV HD）能够更好地诱导 与标准剂量疫苗（IIV SD）相比，活化的pTfh细胞。在这个应用程序中，我们将探讨机制 在老年人群中成功的疫苗免疫反应背后。我们将评估免疫T细胞 老年人巨细胞病毒反应性T细胞的细胞库、应答细胞的转录组学特征和增殖 并确定这些因素对宿主成功免疫的能力的影响 对疫苗的反应。 !

PROJECT SUMMARY We will use cutting edge single T cell analysis techniques to molecularly define the T cell repertoire and function of cellular immune responses of individuals 65 years of age or older. The mechanisms behind declining immune responses with age is likely multifactorial. Aging is associated with a reduction in the frequency of antibody secreting cells and the number of lymph node germinal centers, and we hypothesize this to be due to impaired ability of CD4+ T cells to provide adequate help to B cells. T follicular helper cells in germinal centers directly provide help to B cells, and induce them to become antibody-secreting plasma cells. We have previously demonstrated the frequencies of activated peripheral T follicular helper cells (pTfh) and circulating plasmablasts shortly after vaccination is directly related to subsequent titers of vaccine-specific antibodies. Furthermore, high dose influenza vaccine (IIV HD) was better able to induce activated pTfh cells than standard dose vaccine (IIV SD). In this application we will probe the mechanisms behind successful immune responses to vaccines in an elderly population. We will evaluate the immune T cell repertoire, the transcriptomic profile of responding cells, and inflation of CMV-reactive T cells in elderly individuals and determine the effect of these factors on the host's ability to mount successful immune responses to vaccines. !