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

Jeffrey Pido-Lopez, Nesrina Imami, Deborah Andrew, Richard Aspinall

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 TCRδ DNA locus from within the TCRα chain genes. In αβ+ T cells such δ excision circles (δEC) 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 αβ+ 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 αβ+ T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of αβ+TCR cells possessing δEC 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.

Original languageEnglish
Pages (from-to)2827-2836
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number10
Early online date24 Sep 2002
DOIs
Publication statusPublished - Oct 2002
Externally publishedYes

Fingerprint

T-Lymphocytes
Interleukin-7
Thymus Gland
mouse interleukin-7
Atrophy
Weight Loss
Cell Count
Phenotype
DNA
Population
Genes

Keywords

  • Aging
  • IL-7
  • Recent thymic migrant
  • T cell development
  • Thymus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Molecular quantitation of thymic output in mice and the effect of IL-7. / Pido-Lopez, Jeffrey; Imami, Nesrina; Andrew, Deborah; Aspinall, Richard.

In: European Journal of Immunology, Vol. 32, No. 10, 10.2002, p. 2827-2836.

Research output: Contribution to journalArticle

Pido-Lopez, Jeffrey ; Imami, Nesrina ; Andrew, Deborah ; Aspinall, Richard. / Molecular quantitation of thymic output in mice and the effect of IL-7. In: European Journal of Immunology. 2002 ; Vol. 32, No. 10. pp. 2827-2836.
@article{221b098a867a456793cc7ddfaaa47544,
title = "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 TCRδ DNA locus from within the TCRα chain genes. In αβ+ T cells such δ excision circles (δEC) 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 αβ+ 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 αβ+ T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of αβ+TCR cells possessing δEC 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.",
keywords = "Aging, IL-7, Recent thymic migrant, T cell development, Thymus",
author = "Jeffrey Pido-Lopez and Nesrina Imami and Deborah Andrew and Richard Aspinall",
year = "2002",
month = "10",
doi = "10.1002/1521-4141(2002010)32:10<2827::AID-IMMU2827>3.0.CO;2-X",
language = "English",
volume = "32",
pages = "2827--2836",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley",
number = "10",

}

TY - JOUR

T1 - Molecular quantitation of thymic output in mice and the effect of IL-7

AU - Pido-Lopez, Jeffrey

AU - Imami, Nesrina

AU - Andrew, Deborah

AU - Aspinall, Richard

PY - 2002/10

Y1 - 2002/10

N2 - 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 TCRδ DNA locus from within the TCRα chain genes. In αβ+ T cells such δ excision circles (δEC) 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 αβ+ 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 αβ+ T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of αβ+TCR cells possessing δEC 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.

AB - 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 TCRδ DNA locus from within the TCRα chain genes. In αβ+ T cells such δ excision circles (δEC) 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 αβ+ 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 αβ+ T cells in the peripheral T cell pool altered the component subsets. Mice treated with IL-7 showed increases in the number of αβ+TCR cells possessing δEC 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.

KW - Aging

KW - IL-7

KW - Recent thymic migrant

KW - T cell development

KW - Thymus

UR - http://www.scopus.com/inward/record.url?scp=0036772766&partnerID=8YFLogxK

U2 - 10.1002/1521-4141(2002010)32:10<2827::AID-IMMU2827>3.0.CO;2-X

DO - 10.1002/1521-4141(2002010)32:10<2827::AID-IMMU2827>3.0.CO;2-X

M3 - Article

VL - 32

SP - 2827

EP - 2836

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -