Health Sciences North Research Institute, Sudbury, ON, Canada.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Clin Exp Immunol. 2021 Jul;205(1):63-74. doi: 10.1111/cei.13593. Epub 2021 Apr 4.
Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6 CD14 monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1β, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1β CD14 monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1β CD14 monocytes were significant mediators of the associations between IL-1β and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1β monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6 CD14 monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.
先前的研究表明，T 细胞群的状态和炎症相关因素与水痘带状疱疹病毒（VZV）疫苗在老年人中的免疫原性有关；然而，对于其他已知影响免疫记忆产生和维持的免疫细胞亚群的作用知之甚少。在 30 名养老院居民（年龄 80-99 岁）的样本中，研究了与外周血单核细胞（PBMC）组成和功能相关的活减毒 VZV 疫苗的反应。使用干扰素-γ酶联免疫斑点（ELISPOT）在接种疫苗前后 6 周测量 VZV 反应，并寻求与单核细胞和 T、B 和自然杀伤（NK）细胞的频率以及它们与不同试剂体外刺激后的细胞因子产生和分泌之间的关联。虽然只有白细胞介素（IL）-6 CD14 单核细胞的频率与接种后 VZV 反应呈负相关，但 PBMC 分泌的白细胞介素-1β、白细胞介素-10、白细胞介素-17A 和肿瘤坏死因子（TNF）的量以及 IL-1β CD14 单核细胞的频率与接种前 VZV 反应呈正相关。此外，双变量相关和因果中介分析均支持以下观点，即 IL-1β CD14 单核细胞是 PBMC 中 IL-1β 和 TNF 分泌与接种前 VZV 反应之间关联的重要介质。我们的研究结果表明，由炎症性 IL-1β 单核细胞介导的强烈细胞因子反应在协调长寿 VZV 反应性记忆 T 细胞的反应中起重要作用，但 IL-6 CD14 单核细胞的作用相反。单核细胞状态是否促进或抑制这些记忆 T 细胞在以后的生活中的诱导和/或维持仍有待确定。
