|
|
Blood, 15 March 2007, Vol. 109, No. 6, pp. 2529-2537.
Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-08-043794.
 Previous Article | Next Article 
Submitted August 28, 2006
Accepted October 12, 2006
Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging
Dullei Min, Angela Panoskaltsis-Mortari, Makoto Kuro-o, George A. Hollander, Bruce R. Blazar, and Kenneth I. Weinberg*
Division of Stem Cell Transplantation, Dept of Pediatrics, Stanford University, Stanford, CA, United States
Division of Pediatric Bone Marrow Transplantation, and Cancer Center, University of Minnesota, Minneapolis, MN, United States
Dept of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States
Pediatric Immunology, Department of Research and Clinical-Biological Sciences, University of Basel, Basel, Switzerland
* Corresponding author; email: kw1{at}stanford.edu.
Age-related thymopoietic insufficiency has been proposed to be related to either defects in lymphohematopoietic progenitors or the thymic microenvironment. In this study, we examined whether keratinocyte growth factor (KGF), an epithelial cell-specific growth factor, could increase thymopoietic capacity in aged mice by restoration of the function of thymic epithelial cells (TEC). The thymic cellularity in KGF-treated aged mice increased about 4-fold compared to placebo-treated mice, resulting in an equivalent thymic cellularity to young mice. Enhanced thymopoiesis was maintained for about 2 months after a single course of KGF, and sustained improvement was achieved by administration of monthly courses of KGF. With the enhanced thymopoiesis after KGF treatment, the number of naive CD4 T cells in the periphery and T-cell dependent antibody production improved in aged mice. KGF induced increased numbers of TEC and intrathymic interleukin-7 (IL-7) production and reorganization of cortical and medullary architecture. Furthermore, KGF enhanced thymopoiesis and normalized TEC organization in klotho (kl/kl) mice, a model of premature degeneration and aging, which displays thymopoietic defects. The result suggests that TEC damage is pathophysiologically important in thymic aging, and KGF therapy may be clinically useful in improving thymopoiesis and immune function in the elderly.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. M. Kelly, S. L. Highfill, A. Panoskaltsis-Mortari, P. A. Taylor, R. L. Boyd, G. A. Hollander, and B. R. Blazar
Keratinocyte growth factor and androgen blockade work in concert to protect against conditioning regimen-induced thymic epithelial damage and enhance T-cell reconstitution after murine bone marrow transplantation
Blood,
June 15, 2008;
111(12):
5734 - 5744.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Guimond, W. J. Leonard, R. Spolski, S. W. Rossi, R. G. Veenstra, G. A. Hollander, C. L. Mackall, and B. R. Blazar
Thymic stromal lymphopoietin is not necessary or sufficient to mediate the thymopoietic effects of keratinocyte growth factor
Blood,
January 15, 2008;
111(2):
969 - 970.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. V. Komanduri, L. S. St. John, M. de Lima, J. McMannis, S. Rosinski, I. McNiece, S. G. Bryan, I. Kaur, S. Martin, E. D. Wieder, et al.
Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing
Blood,
December 15, 2007;
110(13):
4543 - 4551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bruinsma, P. L. van Soest, P. J. M. Leenen, B. N. Lambrecht, T. Cupedo, B. Lowenberg, J. J. Cornelissen, and E. Braakman
Keratinocyte Growth Factor Induces Expansion of Murine Peripheral CD4+Foxp3+ Regulatory T Cells and Increases Their Thymic Output
J. Immunol.,
December 1, 2007;
179(11):
7424 - 7430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Chung, E. P. Dudl, D. Min, L. Barsky, N. Smiley, and K. I. Weinberg
Prevention of graft-versus-host disease by anti IL-7R{alpha} antibody
Blood,
October 15, 2007;
110(8):
2803 - 2810.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
