IL-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice

D. Andrew, R. Aspinall

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR β-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) thymocyte development. Because there is no age-associated decrease in the number of CD44+CD25-CD3-CD4-CD8 - cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44+CD25+ and CD44-CD25+ subpopulations, known to be the location of TCR β-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44+CD25+ and CD44-CD25+ subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR β-chain rearrangement.

Original languageEnglish
Pages (from-to)1524-1530
Number of pages7
JournalJournal of Immunology
Volume166
Issue number3
DOIs
Publication statusPublished - 1 Feb 2001
Externally publishedYes

Fingerprint

Interleukin-7
Stem Cell Factor
Apoptosis
Thymocytes
Cell Lineage
Atrophy
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

IL-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice. / Andrew, D.; Aspinall, R.

In: Journal of Immunology, Vol. 166, No. 3, 01.02.2001, p. 1524-1530.

Research output: Contribution to journalArticle

@article{34aa2e51590947448495d98cf67e6cea,
title = "IL-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice",
abstract = "Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR β-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) thymocyte development. Because there is no age-associated decrease in the number of CD44+CD25-CD3-CD4-CD8 - cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44+CD25+ and CD44-CD25+ subpopulations, known to be the location of TCR β-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44+CD25+ and CD44-CD25+ subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR β-chain rearrangement.",
author = "D. Andrew and R. Aspinall",
year = "2001",
month = "2",
day = "1",
doi = "10.4049/jimmunol.166.3.1524",
language = "English",
volume = "166",
pages = "1524--1530",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - IL-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice

AU - Andrew, D.

AU - Aspinall, R.

PY - 2001/2/1

Y1 - 2001/2/1

N2 - Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR β-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) thymocyte development. Because there is no age-associated decrease in the number of CD44+CD25-CD3-CD4-CD8 - cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44+CD25+ and CD44-CD25+ subpopulations, known to be the location of TCR β-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44+CD25+ and CD44-CD25+ subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR β-chain rearrangement.

AB - Thymic atrophy is an age-associated decline in commitment to the T cell lineage considered to be associated with defective TCR β-chain rearrangement. Both IL-7 and stem cell factor (SCF) have dominant roles at this stage of triple negative (TN) thymocyte development. Because there is no age-associated decrease in the number of CD44+CD25-CD3-CD4-CD8 - cells, this study investigated whether alterations in apoptosis within the TN pathway accounted for diminishing thymocyte numbers with age. Here we show significant age-associated increases in apoptotic TN thymocytes, specifically within CD44+CD25+ and CD44-CD25+ subpopulations, known to be the location of TCR β-chain rearrangement. IL-7 added to TN cultures established from old mice significantly both reduces apoptosis and increases the percentage of live cells within CD44+CD25+ and CD44-CD25+ subpopulations after 24 h, with prosurvival effects remaining after 5 days. SCF failed to demonstrate prosurvival effects in old or young cultures, and IL-7 and SCF together did not improve upon IL-7 alone. IL-7R expression did not decline with age, ruling out the possibility that the age-associated increase in apoptosis was attributed to reduced IL-7R expression. Compared with PBS, treatment of old mice with IL-7 produced significant increases in live TN cells. By comparison, treatment with SCF failed to increase live TN numbers, and IL-7 and SCF together failed to significantly improve thymopoiesis above that shown by IL-7 alone. Thus, treatment with IL-7 alone can reverse the age-associated defect in TN thymocyte development revealed by in vitro studies to be located at the stages of TCR β-chain rearrangement.

UR - http://www.scopus.com/inward/record.url?scp=0035253734&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.166.3.1524

DO - 10.4049/jimmunol.166.3.1524

M3 - Article

VL - 166

SP - 1524

EP - 1530

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -