Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution.
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.
Zhu
Xike
X
Department of Biomedical Research, University of Texas Health Center at Tyler, Tyler, TX 75708, USA.
Gui
Jingang
J
Dohkan
Junichi
J
Cheng
Lili
L
Barnes
Peter F
PF
Su
Dong-Ming
DM
D000375:Aging; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D016332:Fetal Tissue Transplantation; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D054504:Precursor Cells, T-Lymphoid / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000502:physiology* / Q000637:transplantation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte