Molecular quantitation of thymic output in mice and the effect of IL-7.

Abstract

Aging of the murine thymus is accompanied by a measurable loss of weight and cellularity and a marked reduction in its output of T lymphocytes. This study employs a molecular approach to determine changes in the output of the murine thymus using a novel assay system based on the detection and quantitation of the excised TCRdelta DNA locus from within the TCRalpha chain genes. In alpha beta(+) T cells such delta excision circles (deltaEC) are present at higher levels in naive T cells as compared with memory T cell populations, are non-replicating, and diluted within the total peripheral alpha beta(+) T cell pool with advancing age. This assay permits the assessment of thymic output in older animals where previous analysis was hampered by the transient nature of the naive T cell surface phenotype, and so allows the assessment of the efficacy of IL-7 as an agent to reverse thymic atrophy. Treatment of old mice with IL-7 although producing no overall change in the total number of alpha beta(+) T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of alpha beta(+)TCR cells possessing deltaEC commensurate with improved thymic output, and the splenic T cells from IL-7-treated mice performed significantly better in in vitro functional assays compared to those from age-matched saline-treated controls.