Research Paper Volume 4, Issue 9 pp 606—619

Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus

Liguang Sun1,3, *,, Robert Brown4, *,, Shande Chen2, , Qichuan Zhuge5, , Dong-Ming Su1,5, ,

  • 1 Department of Molecular Biology and Immunology, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA
  • 2 Department of Biostatics, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA
  • 3 Institute of Translational Medicine, Norman Bethune First Hospital, Jilin University, Changchun City, 135505, China
  • 4 University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA
  • 5 The First Affiliated Hospital, Wenzhou Medical College, Wenzhou city, Zhejiang Province, 325000, China
* Equal contribution

Received: October 5, 2012       Accepted: October 7, 2012       Published: October 8, 2012      

https://doi.org/10.18632/aging.100487
How to Cite

Abstract

Age-related decline in the generation of T cells is associated with two primary lymphoid organs, the bone marrow (BM) and thymus. Both organs contain lympho-hematopoietic progenitor/stem cells (LPCs) and non-hematopoietic stromal/niche cells. Murine model showed this decline is not due to reduced quantities of LPCs, nor autonomous defects in LPCs, but rather defects in their niche cells. However, this viewpoint is challenged by the fact that aged BM progenitors have a myeloid skew. By grafting young wild-type (WT) BM progenitors into aged IL-7R−/− hosts, which possess WT-equivalent niches although LPCs are defect, we demonstrated that these young BM progenitors also exhibited a myeloid skew. We, further, demonstrated that aged BM progenitors, recruited by a grafted fetal thymus in the in vivo microenvironment, were able to compete with their young counterparts, although the in vitro manipulated old BM cells were not able to do so in conventional BM transplantation. Both LPCs and their niche cells inevitably get old with increasing organismal age, but aging in niche cells occurred much earlier than in LPCs by an observation in thymic T-lymphopoiesis. Therefore, the aging induced decline in competence to generate T cells is primarily dependent on status of the progenitor niche cells in the BM and thymus.

Abbreviations

BMT: bone marrow transplantation; FTOC: fetal thymic organ culture; KCT: kidney capsule transplantation; LPC/HSC: lympho-hematopoietic progenitor cell/hematopoietic stem cell; LSK: lineage-negative, Sca1-positive, cKit-positive population; TEC: thymic epithelial cell; WT: wild type.