T-cell maintenance in homeostasis: Insights from labeling, modeling, and repertoire analysis

Abstract

In this thesis we investigate the population dynamics and T-cell receptor (TCR) diversity of several T-cell subsets including tissue resident memory and regulatory T cells in humans and mice. In Chapters 2 and 3, we propose improvements to the data processing and mathematical modeling of deuterium labeling experiments which are widely used to estimate turnover rates of the T-cell populations. In the second part, we demonstrate that tissue resident memory T cells and regulatory T cells exhibit faster turnover than naive T cells. Measuring TCR repertoire diversity across age groups reveals that aging impacts TCR diversity more profoundly than neonatal thymectomy. Additionally, we found considerable overlaps in TCR repertoires between memory and regulatory T cells, which suggests a shared developmental origin. Overall, this work provides quantitative insights into T-cell homeostasis and immune memory, which improves our understanding of immune health during aging and disease.