Maintenance of peripheral naive T cells: a mouse-man divide (159.1)

Abstract Insights from T-cell dynamic studies in mice are widely extrapolated to men and vice versa, while no formal proof exists that such extrapolations are justified. At the same time, there is a lot of controversy about the dynamic properties of T cells, including life span and the relative contributions of thymus output and peripheral proliferation to the maintenance of the naive T-cell pool during aging. We have investigated the hypothesis that part of this controversy is due to improper extrapolation of dynamic parameters of T cells from mice to men. By combining in vivo kinetic labeling using deuterated water, thymectomy experiments, analysis of TRECs, the expression of the thymic proximity marker CD31, and mathematical modeling, we have quantified the contributions of de novo T-cell production by the thymus and peripheral naive T-cell division to life-long maintenance of the naive T-cell pool in both mice and men under normal physiological conditions. Our results show that mice and men are incomparable with respect to naive T-cell maintenance. While in mice - throughout their life time - the naive T-cell pool is almost exclusively sustained by thymus output, the maintenance of the adult human naive T-cell pool occurs almost exclusively through peripheral T-cell division. These findings put serious constraints on the use of mouse experiments to understand immunological processes such as T-cell reconstitution in lymphopenic patients or the effects of aging in healthy humans.