Broadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges. Further exploration of these relationships may be useful for informing personalized intervention development. To address this need, we evaluated 41 different cell type frequencies by mass cytometry and identified their relationships with aging and CMV seropositivity. Analyses were done using 60 healthy individuals, including 23 monozygotic twin pairs, categorized into young (12–31 years) and middle-aged (42–59 years). Aging and CMV discordance were associated with increased immune diversity between monozygotic twins overall, and particularly strongly in various T cell populations. Notably, we identified 17 and 11 cell subset frequencies as relatively influenced and uninfluenced by non-heritable factors, respectively, with results that largely matched those from studies on older-aged cohorts. Next, CD4+ T cell frequency was shown to diverge with age in twins, but with lower slope than in demographically similar non-twins, suggesting that much inter-individual variance in this cell type can be attributed to interactions between genetic and environmental factors. Several cell frequencies previously associated with memory inflation, such as CD27- CD8+ T cells and CD161+ CD4+ T cells, were positively correlated with CMV seropositivity, supporting findings that CMV infection may incur rapid aging of the immune system. Our study confirms previous findings that aging, even within a relatively small age range and by mid-adulthood, and CMV seropositivity, both contribute significantly to inter-individual immune diversity. Notably, we identify several key immune cell subsets that vary considerably with aging, as well as others associated with memory inflation which correlate with CMV seropositivity.

中文翻译：

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衰老和CMV不一致与单卵双胞胎之间的免疫多样性增加有关

广泛地讲，免疫系统表型的许多差异都与非遗传因素而不是遗传因素有关。特别是，已知两个不可遗传的因素：衰老和人巨细胞病毒（CMV）感染是造成个体间重大免疫变异的原因。但是，它们与免疫组成之间的许多具体关系仍然不清楚，尤其是在年龄范围较小的个体之间。这些关系的进一步探索对于通知个性化干预发展可能是有用的。为了满足这一需求，我们通过质谱分析评估了41种不同的细胞类型频率，并确定了它们与衰老和CMV血清阳性之间的关系。使用60位健康个体（包括23对单卵双生子对）进行了分析，分为青年（12-31岁）和中年（42-59岁）。总体而言，衰老和CMV不一致性与单卵双胞胎之间免疫多样性的增加有关，尤其是在各种T细胞群体中。值得注意的是，我们分别确定了17和11个细胞子集频率分别受非遗传因素的相对影响和不受其影响，其结果与老年人群的研究结果基本相符。其次，双胞胎的CD4 + T细胞频率显示随着年龄的变化而发散，但比人口统计学上相似的非双胞胎的斜率低，这表明这种细胞类型的个体差异很大是由于遗传和环境因素之间的相互作用。先前与记忆膨胀相关的几种细胞频率，例如CD27- CD8 + T细胞和CD161 + CD4 + T细胞，与CMV血清阳性呈正相关，支持了CMV感染可能导致免疫系统快速老化的发现。我们的研究证实了以前的发现，即衰老，即使是在相对较小的年龄范围内，到成年中期，以及CMV血清阳性也都对个体间的免疫多样性做出了重要贡献。值得注意的是，我们确定了几个关键的免疫细胞亚群，这些亚群随年龄的变化而变化很大，还有其他一些与与CMV血清阳性相关的记忆充盈相关。