TY - JOUR
T1 - Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution
AU - Zhu, Xike
AU - Gui, Jingang
AU - Dohkan, Junichi
AU - Cheng, Lili
AU - Barnes, Peter F.
AU - Su, Dong Ming
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
KW - Hematopoietic stem cells
KW - Microenvironment
KW - T-cell development
KW - Thymic aging
UR - http://www.scopus.com/inward/record.url?scp=34548637281&partnerID=8YFLogxK
U2 - 10.1111/j.1474-9726.2007.00325.x
DO - 10.1111/j.1474-9726.2007.00325.x
M3 - Article
C2 - 17681038
AN - SCOPUS:34548637281
SN - 1474-9718
VL - 6
SP - 663
EP - 672
JO - Aging Cell
JF - Aging Cell
IS - 5
ER -