Tu184 - Analysis of Healthy Adult Immunotypes Reveals Young Female Cohort with Elevated Inflammatory Response to Truculture Stimulation

Alex Hu – Benaroya Research Institute; Matthew Dufort – Benaroya Research Institute; Alyssa Ylescupidez – Benaroya Research Institute; Alice Wiedeman – Benaroya Research Institute; Carolina Acosta-Vega – Benaroya Research Institute; Sheila Scheiding – Benaroya Research Institute; Grace De Castro – Benaroya Research Institute; Thomas Bumol – The Allen Institute for Immunology; Lynne Becker – The Allen Institute for Immunology; Troy Torgerson – The Allen Institute for Immunology; Xiaojun Li – The Allen Institute for Immunology; Qiuyu Gong – The Allen Institute for Immunology; Claire Gustafson – The Allen Institute for Immunology; Jane Buckner – Benaroya Research Institute; Cate Speake – Benaroya Research Institute

Abstract Text: The frequencies of many circulating immune cells are stable over time but vary between healthy individuals, suggesting the presence of diverse stable immunotypes. The relationship between immunotype and immune response kinetics and character is poorly understood. We measured circulating immune cells in a cohort of 100 adults with no history of chronic disease, aged 25-35 and 55-65. These individuals were followed approximately every three months for two years, allowing us to characterize between- and within-subject variation in immune cell frequency. We identified cell populations with an intraclass correlation coefficient above 0.5, and used them to cluster individuals revealing four immunotypes dominated by older adults (n=30), younger adults (n=19), CMV+ adults from both age cohorts (n=31), and, surprisingly, a group of young female participants (n=20). This cluster was defined by low levels of NK cells and high levels of naïve CD4+ T cells and central memory CD8+ T cells. Compared to other young adults, they had elevated levels of neutrophils and basophils. To investigate the relationship between immunotype and immune response, we performed RNAseq on whole blood samples stimulated with LPS, SEB, PolyI:C, R848, and IL1β+TNFα. We found that participants in the young female cluster had elevated inflammatory responses to LPS, IL1β+TNFα, and R848.. These findings highlight the diversity of immunotypes and their role in driving immune responses even among healthy adults and may be useful in understanding the influence of sex, age, and immune history in response to infection.