07/01/2025
The aim of the paper is to assess and quantify age-related homeostasis for a wide range of total T cells and specific T cell subsets in healthy individuals.
To gain a deeper understanding of the problem, a systematic literature review was conducted to identify and collect relevant quantitative information on T cell counts in human blood and various organs. Both individual subject data and aggregated T cell observations in absolute and relative values were digitized and processed; cellular phenotypes, gating strategies for flow cytometry analysis, organs from which observations were obtained, number of subjects, and age were systematically inventoried. Age-related homeostasis of each T cell subset was estimated by calculating a weighted average within predefined age intervals using piecewise uniform meta-analysis methodology.
The results of a total of 124 studies, comprising 11,722 unique observations from healthy subjects, covering 20 different T-cell subsets – total CD45+ and CD3+ lymphocytes, as well as specific CD4+ and CD8+ naive, recent thymic immigrant, activated, effector and various memory T-cell subsets (total memory, central memory, effector memory, resident memory) – were systematically collected and included in a final database for comprehensive analysis. Blood counts of most T-cell subsets show a decline with age, with a pronounced decline during the first 10 years of life. In contrast, memory T-cells show a trend to increase in older age groups, especially after ~50 years. Notably, the increase in T cell numbers is observed in neonates and infants (0–1 year of age) towards less differentiated T cell subsets, while the increase in more differentiated subsets appears later (1–5 years of age).
In summary, a comprehensive systematic review and meta-analysis of age-dependent T cell homeostasis in healthy individuals was conducted to assess immune T cell profiles as a function of age and to characterize pooled estimates of T cell numbers across age groups. Our study provides a quantitative description of the fundamental parameters characterizing the maintenance and evolution of T cell subsets with age based on a comprehensive integration of available organ- and system-specific flow cytometry datasets. Overall, it provides the most up-to-date understanding of T cell physiological dynamics and its dispersion and can be used as a consistent reference to gain further mechanistic understanding of human immune status in health and disease.
