Thymic Output in Aged Mice

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 decl...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-05, Vol.103 (22), p.8447-8452
Main Authors: Hale, J. Scott, Boursalian, Tamar E., Turk, Gail L., Fink, Pamela J.
Format: Article
Language:English
Subjects:
Age
Aging
Aging - immunology
Animals
Biological Sciences
CD4-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - cytology
Cell Movement
Cell Proliferation
Cells
Cells, Cultured
Genes
Histograms
Immunity, Innate
Kinetics
Lymphatic system
Lymphocyte Count
Mice
Organ Size
Phenotype
Rodents
Spleen
Splenocytes
T cell antigen receptors
T cell receptors
T lymphocytes
Thymocytes
Thymus Gland - cytology
Thymus Gland - immunology
Young adults
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Summary: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 earlyactivation 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0601040103