Maintenance of Peripheral Naive T Cells Is Sustained by Thymus Output in Mice but Not Humans

SummaryParallels between T cell kinetics in mice and men have fueled the idea that a young mouse is a good model system for a young human, and an old mouse, for an elderly human. By combining in vivo kinetic labeling using deuterated water, thymectomy experiments, analysis of T cell receptor excision circles and CD31 expression, and mathematical modeling, we have quantified the contribution of thymus output and peripheral naive T cell division to the maintenance of T cells in mice and men. Aging affected naive T cell maintenance fundamentally differently in mice and men. Whereas the naive T cell pool in mice was almost exclusively sustained by thymus output throughout their lifetime, the maintenance of the adult human naive T cell pool occurred almost exclusively through peripheral T cell division. These findings put constraints on the extrapolation of insights into T cell dynamics from mouse to man and vice versa.

► Mice and men are incomparable with respect to their naive T cell maintenance ► Naive T cell maintenance in human adults occurs primarily by cell division ► Throughout life, the naive T cell pool in mice is sustained by thymus output ► In men, naive T cells live 6–10 years, whereas in mice, they live 6–10 weeks