Abstract Text: Immune perturbations induce diverse responses in healthy adults that are not entirely predicted by demographics. We and others have shown that the frequencies of many circulating immune cells 1) can be predictive of response to vaccination or disease 2), are highly variable between healthy adults but stable over time within individuals, and 3) return to baseline after an immune challenge. Our goal was to interrogate variations in immune baselines among healthy adults across different age groups to understand the functional impacts of natural variation of the healthy human immune system. To do this, we modeled the breadth of immune phenotypes (immunotypes) in a cohort of 100 healthy adults, half aged 25-35 and half aged 55-65 years. We quantified circulating immune cell frequencies of 54 cell types measured using mass cytometry at 10 visits over two years. We defined immunotypes based on levels of relatively stable immune cell populations at unperturbed visits. Our study design also incorporated immune perturbations including response to influenza immunization. We quantified similarity of participants’ immunotypes using Euclidean distances between participants in multidimensional immunospace at unperturbed visits. Immunotypes were more similar within our younger cohort and more diverse in our older cohort and this was reflected functionally in the response to polyIC stimulation (TruCulture) and flu vaccination. These findings indicate that immune experience may drive increased diversity of immunotypes with age. We are currently expanding this work to investigate the relationship between immunotype and response to environmental factors such as pollen and wildfire.
