Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution

Xike Zhu, Jingang Gui, Junichi Dohkan, Lili Cheng, Peter F. Barnes, Dong Ming Su

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

It has been speculated that aging lymphohematopoietic progenitor cells (LPC) including hematopoietic stem cells (HSC) and early T-cell progenitors (ETP) have intrinsic defects that trigger age-related thymic involution. However, using a different approach, we suggest that that is not the case. We provided a young thymic microenvironment to aged mice by transplanting a fetal thymus into the kidney capsule of aged animals, and demonstrated that old mouse-derived LPCs could re-establish normal thymic lymphopoiesis and all thymocyte subpopulations, including ETPs, double negative subsets, double positive, and CD4+ and CD8+ single positive T cells. LPCs derived from aged mice could turn over young RAG-/- thymic architecture by interactions, as well as elevate percentage of peripheral CD4+ IL-2+ T cells in response to costimulator in aged mice. Conversely, intrathymic injection of ETPs sorted from young animals into old mice did not restore normal thymic lymphopoiesis, implying that a shortage and/or defect of ETPs in aged thymus do not account for age-related thymic involution. Together, our findings suggest that the underlying cause of age-related thymic involution results primarily from changes in the thymic microenvironment, causing extrinsic, rather than intrinsic, defects in T-lymphocyte progenitors.

Original languageEnglish
Pages (from-to)663-672
Number of pages10
JournalAging Cell
Volume6
Issue number5
DOIs
StatePublished - 1 Oct 2007

Fingerprint

Lymphopoiesis
T-Lymphocytes
Thymus Gland
Thymocytes
Hematopoietic Stem Cells
Capsules
Interleukin-2
Stem Cells
Kidney
Injections

Keywords

  • Hematopoietic stem cells
  • Microenvironment
  • T-cell development
  • Thymic aging

Cite this

Zhu, Xike ; Gui, Jingang ; Dohkan, Junichi ; Cheng, Lili ; Barnes, Peter F. ; Su, Dong Ming. / Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution. In: Aging Cell. 2007 ; Vol. 6, No. 5. pp. 663-672.
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Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution. / Zhu, Xike; Gui, Jingang; Dohkan, Junichi; Cheng, Lili; Barnes, Peter F.; Su, Dong Ming.

In: Aging Cell, Vol. 6, No. 5, 01.10.2007, p. 663-672.

Research output: Contribution to journalArticle

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