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A high-dimensional cytometry atlas of peripheral blood over the human life span
Sedigheh Jalali1,2, Christopher M Harpur1, Adam T Piers1,3
1Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Insights
This study maps the human immune system from birth to age 75, revealing key changes in immune cell populations during childhood and adulthood. Understanding these shifts in immune cells is crucial for disease susceptibility and developing targeted therapies.
Area of Science:
- Immunology
- Human Physiology
- Computational Biology
Background:
- Age significantly impacts disease susceptibility and severity.
- The developing immune system in children is not well understood compared to adults.
- Immune cell composition is a key factor in disease outcomes.
Purpose of the Study:
- To create a comprehensive immune cell atlas of the healthy human immune system across the lifespan (birth to 75 years).
- To identify age-specific changes in immune cell populations, particularly in children.
- To provide a reference for understanding immune system dynamics in health and disease.
Main Methods:
- Utilized high-dimensional spectral flow cytometry to analyze over 50 immune cell populations.
- Employed computational methods for data integration to build the immune cell atlas.
- Focused analysis on peripheral blood samples from individuals across a wide age range.
Main Results:
- Identified distinct patterns of immune cell changes from infancy through adolescence.
- Specific immune cells (e.g., CD4+ T effector memory, Vδ2+ γδT, NK cells) showed age-specific peaks in childhood (5-18 years).
- Observed unique immune cell profiles in early adulthood and late adulthood, including changes in T cells, B cells, and NK cells.
Conclusions:
- The developed immune cell atlas provides a vital resource for understanding human immune system development and aging.
- This atlas serves as a reference for investigating immune responses in various diseases.
- Findings may inform the development of targeted immunotherapies for different age groups.
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 coronavirus disease 2019 and hepatitis A, they are more protected compared with 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 analyzed more than 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+ T effector memory cells, Vδ2+ gamma delta (γδ)T cells, memory B cells, plasmablasts, CD11c+ B cells and CD16+ CD56bright natural killer (NK) cells peaked in children aged 5-9 years old, whereas frequencies of T helper 1, T helper 17, dendritic cells and CD16+ CD57+ CD56dim NK cells were highest in older children (10-18 years old). The frequency of mucosal-associated invariant T 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 mucosal-associated invariant T cells and Vδ2+ γδ 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.
