Upon thymus entry, thymic-homing progenitors undergo distinct phases of differentiation as they migrate through the cortex to the capsule, suggesting that the signals that induce these differentiation steps may be stratified in corresponding cortical regions. To better define these regions, we transplanted purified stem cells into nonirradiated congenic recipients and followed their differentiation with respect to both tissue location and time. The earliest progenitors (DN1) remained confined to a very narrow region of the cortex for about the first 10 d of intrathymic residence; this region virtually overlaps the sites of thymic entry, suggesting that DN1 cells move very little during this lengthy period of proliferation and lineage commitment. Movement out of this region into the deeper cortex is asynchronous, and corresponds to the appearance of DN2 cells. Differentiation to the DN3 stage correlates with movement across the midpoint of the cortex, indicating that stromal signals that induce functions such as TCR gene rearrangement reside mainly in the outer half of the cortex. The minimum time to reach the capsule, and thus transit to the DP stage, is ∼13 d, with the average time a few days longer. These findings reveal for the first time the kinetics of steady-state progenitor differentiation in the thymus, as well as defining the boundaries of cortical regions that support different phases of the differentiation process. We also show that the first lineage-positive progeny of transplanted stem cells to appear in the thymus are dendritic cells in the medulla, suggesting that each new wave of new T cell production is preceded by a wave of regulatory cells that home to the medulla and ensure efficient tolerance and selection.
Skip Nav Destination
Article navigation
15 September 2003
Brief Definitive Report|
September 15 2003
Kinetics of Steady-state Differentiation and Mapping of Intrathymic-signaling Environments by Stem Cell Transplantation in Nonirradiated Mice
Helen E. Porritt,
Helen E. Porritt
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Search for other works by this author on:
Kristie Gordon,
Kristie Gordon
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Search for other works by this author on:
Howard T. Petrie
Howard T. Petrie
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021
2Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021
Search for other works by this author on:
Helen E. Porritt
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Kristie Gordon
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021
Howard T. Petrie
1Memorial Sloan-Kettering Cancer Center, New York, NY 10021
2Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021
Address correspondence to Howard T. Petrie, Memorial Sloan-Kettering Box 341, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-2149; Fax: (212) 794-4019; email: [email protected]
Abbreviation used in this paper: HSC, hematopoietic stem cell.
Received:
May 21 2003
Revision Received:
June 30 2003
Accepted:
August 04 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (6): 957–962.
Article history
Received:
May 21 2003
Revision Received:
June 30 2003
Accepted:
August 04 2003
Citation
Helen E. Porritt, Kristie Gordon, Howard T. Petrie; Kinetics of Steady-state Differentiation and Mapping of Intrathymic-signaling Environments by Stem Cell Transplantation in Nonirradiated Mice . J Exp Med 15 September 2003; 198 (6): 957–962. doi: https://doi.org/10.1084/jem.20030837
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement