Open AccessLymphohematopoietic progenitors do not have a synchronized defect with age‐related thymic involution
Author(s) -
Zhu Xike,
Gui Jingang,
Dohkan Junichi,
Cheng Lili,
Barnes Peter F.,
Su DongMing
Publication year - 2007
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2007.00325.x
Subject(s) - thymic involution , lymphopoiesis , biology , involution (esoterism) , thymocyte , haematopoiesis , progenitor cell , double negative , cd8 , medicine , stem cell , endocrinology , immunology , t cell , immune system , microbiology and biotechnology , consciousness , neuroscience
Summary 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.