The cellular composition of the human immune system is shaped by age and cohabitation

Abstract

Detailed population-level description of the human immune system has recently become achievable. We used a “systems-level” approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of inter-individual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes being followed by a return to the unique baseline of the individual. Strikingly, the largest influence on immunological variation identified was cohabitation, with a 50% reduction in immunological variation between individuals who share an environment (parents) compared to the wider population. These results identify local environmental conditions are a key shaper of the human immune system.

Continuous immunotypes describe human immune variation and predict diverse responses

“…We analyzed human immune cell frequency data from multiple cohorts, described in further detail in Materials and Methods. These are referred to as the Stanford cohorts of 398 individuals, 226 MZ and dizygotic (DZ) twins from a published twin study (4), 23 individuals from a published longitudinal study (11), and 149 previously unpublished subjects (combined in Dataset S1); the Roederer et al (10) cohort, consisting of 669 female twins sampled in the United Kingdom; and the Carr et al (6) cohort, consisting of 670 nontwin subjects, both men and women, sampled in Belgium.…”

“…We first analyzed immune cell composition data from a total of 1,575 healthy individuals across multiple cohorts, both published (6,10) and previously unpublished (149 individuals) in addition to our previously published data (4), combined in Dataset S1. We also took advantage of a set of diverse functional responses measured in 329 individuals from a number of Stanford cohorts (refs.…”

“…With recent advances in single-cell measurement technologies such as high-dimensional flow cytometry and mass cytometry (2), these different immune cell populations can be simultaneously quantified in an individual sample. Leveraging these developments, recent population studies have profiled the global immune cell composition in healthy adult humans (3)(4)(5) and found these to be highly stable within an individual over the course of weeks to months, but highly variable between individuals (3,6). Although variations in a few immune cell populations are heritable, the majority of immune cell population frequencies and functional responses are largely determined by nonheritable influences in healthy individuals (4).…”

“…Although variations in a few immune cell populations are heritable, the majority of immune cell population frequencies and functional responses are largely determined by nonheritable influences in healthy individuals (4). For example, cohabitation has been shown to be a strong influence, emphasizing the importance of shared environmental factors within a household (6). Most of the specific environmental factors that shape human immune systems have yet to be determined, but monozygotic (MZ) twin pairs discordant for human cytomegalovirus (HCMV) seropositivity were more different in the majority of immune measurements compared with seronegative twins (4).…”

Milieu intérieur: Defining the boundaries of a healthy immune response for improved vaccination strategies

“…1 Depending on the specific immune phenotype studied, up to 50% of the observed variance is estimated to be due to environmental factors, 21 with an estimated 20–40% due to genetics. 22 , 23 However, a striking amount of the specific individual factors behind this variation remains to be defined, and in particular, the specific environmental factors that act to influence immunity.…”