International Immunology Advance Access originally published online on September 5, 2007
International Immunology 2007 19(10):1201-1211; doi:10.1093/intimm/dxm095
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The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells
1 Department of Biomedical Research
2 Center for Pulmonary and Infectious Disease Control, University of Texas Health Center at Tyler, Tyler, TX 75708, USA
3 Present address: Genetic Lab, China Medical University Shengjing Hospital, #36 Sanhao Street, Shenyang 110004, P.R. China
4 Present address: National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3, Gengo, Morioka-cho, Ohbu city, Aichi 474-8522, Japan
Correspondence to: D.-M. Su; E-mail: dong-ming.su{at}uthct.edu
Aging is associated with reduced numbers of all thymocyte sub-populations, including early T-cell progenitors. However, it is unclear if this is due to inadequate recruitment of lymphohematopoietic progenitor cells (LPCs) to the aged thymus or to abnormal development of T cells within the thymus. We found that LPCs from young mice were recruited equally well to the thymi of young or aged mice and that thymic stromal cells (TSCs) from young and old mice expressed similar levels of P-selectin and CCL25, which are believed to mediate recruitment of LPCs to the adult thymus. However, the number of recruited thymocytes in old thymus was markedly reduced after two weeks, indicating that T-cell development or proliferation is defective in the aged thymus. We also found that LPCs from aged and young mice have similar capacities to seed a fetal thymus that was transplanted under the kidney capsule. Thymic epithelial cells (TECs) in aged mice had lower proliferative capacity and higher rate of apoptosis, compared with findings in young animals. In addition, immunofluorescence staining with antibodies to cortical and medullary TECs revealed that aged thymi had a disorganized thymic stromal architecture, combined with reduced cellularity of the medulla, and apoptosis of thymocyte sub-populations in the medullary microenvironment was increased, compared with that in young mice. We conclude that aging does not impair recruitment of LPCs to the thymus, but is characterized by abnormalities in thymic epithelial architecture, especially medullary TEC function that may provide sub-optimal support for thymic development of LPCs.
Keywords: CCL25, progenitor recruitment, proliferation and apoptosis, P-selectin, thymic aging, thymic epithelial cells
* These authors contributed equally to this study.
Transmitting editor: T. Watanabe
Received 30 April 2007, accepted 18 July 2007.
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