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 (80-99 years old). Interferon-gamma 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 NK-cells, and the production and secretion of cytokines following their ex vivo stimulation with different agents. While only the frequency of IL-6 CD14 monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1β, IL-10, IL-17A and 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.
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