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- Title
Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution.
- Authors
Xike Zhu; Jingang Gui; Dohkan, Junichi; Cheng, Lili; Barnes, Peter F.; Dong-Ming Su
- 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.
- Subjects
HEMATOPOIETIC stem cells; T cells; GROWTH factors; AGING; THYMUS
- Publication
Aging Cell, 2007, Vol 6, Issue 5, p663
- ISSN
1474-9718
- Publication type
Article
- DOI
10.1111/j.1474-9726.2007.00325.x