W81 - Mass Cytometry to Define Healthy Immunotypes

Healthy adult immune systems are composed of cell populations that are longitudinally stable within individuals over time, but highly variable between individuals. We hypothesize that these intrinsic inter-individual differences may help explain response to immunotherapy or propensity for development of immune-mediated disease.  Here, we have identified and correlated immune cell populations to describe stable immune baseline phenotypes, or immunotypes, in younger and older healthy adult cohorts.  We obtained longitudinal whole blood samples from 51healthy adults between 25 and 35 years of age and 49 healthy adults between 55 and 65 years of age. All participants reported no history of chronic disease. 10 samples per participant were collected; 4 at timepoints that were not associated with any known immune challenge, and 2 sets of 3 timepoints surrounding vaccination for seasonal influenza.  We used mass cytometry to identify major innate and adaptive immune cell populations. Cell populations were selected based on high within- and low between-individual stability, to identify clusters of features that reliably enable grouping of individuals by immunotype. We describe associations between immunotype and many demographic variables including age, sex, substance use, BMI, and residence history to parse their influence on immunotype. Furthermore, we investigate how response to seasonal flu and COVID-19 vaccination may be influenced by immunotype. These data contribute to our understanding of human immune system variability and lay the groundwork for future studies of immunotype’s influence on disease course and treatment.