Thymic output in aged mice

JS Hale, TE Boursalian, GL Turk… - Proceedings of the …, 2006 - National Acad Sciences
JS Hale, TE Boursalian, GL Turk, PJ Fink
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
Using GFP to mark recent thymic emigrants (RTEs) in mice carrying a GFP transgene driven
by the recombination-activating gene 2 promoter, we demonstrate that RTEs are readily
detectable even in 2-year-old mice, despite the fact that the proportion of the peripheral T
cell pool comprised of RTEs declines with age. Although the number of RTEs decreases
after reaching a peak at 6 weeks of age, thymic output as a function of thymic size is
surprisingly age-independent. The CD4: CD8 ratio of RTEs declines with age, partly …
Using GFP to mark recent thymic emigrants (RTEs) in mice carrying a GFP transgene driven by the recombination-activating gene 2 promoter, we demonstrate that RTEs are readily detectable even in 2-year-old mice, despite the fact that the proportion of the peripheral T cell pool comprised of RTEs declines with age. Although the number of RTEs decreases after reaching a peak at 6 weeks of age, thymic output as a function of thymic size is surprisingly age-independent. The CD4:CD8 ratio of RTEs declines with age, partly because of a striking decrease in steady-state proliferation of CD4+ RTEs in older mice. RTEs in aged mice undergo phenotypic maturation in the lymphoid periphery with delayed kinetics compared with young mice. RTEs from aged mice secrete less IL-2, proliferate less well, and achieve only weak expression of early-activation markers compared with more mature naïve peripheral T cells from the same mice. The proportion of GFP cells in the CD4+ and CD8+ thymic compartments increases with age, partly as a result of leakiness in the aged thymus, allowing reentry of naïve peripheral T cells.
National Acad Sciences