Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

A high-dimensional cytometry atlas of peripheral blood over the human life span.

Abstract

Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible to some infectious diseases such as diphtheria and pertussis, while in others, such as COVID-19 and hepatitis A, they are more protected compared to adults. One explanation is that the composition of the immune system is a major contributing factor to disease susceptibility and severity. While most studies of the human immune system have focused on adults, how the immune system changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry and computational methods for data integration, we analysed > 50 populations of immune cells in the peripheral blood, generating an immune cell atlas that defines the healthy human immune system from birth up to 75 years of age. We focused our efforts on children under 18 years old, revealing major changes in immune cell populations after birth and in children of schooling age. Specifically, CD4+ TEM cells, Vdelta2+ gammadelta T cells, memory B cells, plasmablasts, CD11c+ B cells, and CD16+ CD56bright NK cells peaked in children aged 5-9 years old, while TH1, TH17, dendritic cells, and CD16+ CD57+ CD56dim NK cells frequencies were highest in older children (10-18 years old). The frequency of MAIT cells was low in the first several years of life and highest in adults between 19 and 30 years old. Late adulthood was associated with fewer MAIT cells and Vdelta2+ gammadelta T cells but with increased frequencies of memory subsets of B cells, CD4+ and CD8+ T cells and CD57+ NK cells. This human immune cell atlas provides a critical resource to understand changes to the immune system during life and provides a reference for investigating the immune system in the context of human disease. This work may also help guide future therapies that target specific populations of immune cells to protect at-risk populations.