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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2453-2460.
Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-07-2831.
 Previous Article | Next Article 
Submitted July 18, 2005
Accepted November 8, 2005
Keratinocyte Growth Factor (KGF) Is Required For Post-Natal Thymic Regeneration
Onder Alpdogan, Vanessa M Hubbard, Odette M Smith, Neel Patel, Sydney X Lu, Gabrielle L Goldberg, Daniel H Gray, Jared Feinman, Adam A Kochman, Jeffrey M Eng, Stephanie J Muriglan, David Suh, Richard L Boyd, and Marcel R van den Brink*
Departments of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Departments of Pathology and Immunology, Monash University Medical School, Melbourne, Victoria, Australia
* Corresponding author; email: vandenbm{at}mskcc.org.
Keratinocyte Growth Factor (KGF) is a member of the fibroblast growth factor family that mediates epithelial cell proliferation and differentiation in a variety of tissues, including the thymus. We studied the role of KGF in T cell development with KGF (-/-) mice and demonstrated that thymic cellularity and the distribution of thymocyte subsets among KGF (-/-), wild type (WT), and KGF (+/-) mice were similar. However, KGF (-/-) mice are more vulnerable to sublethal irradiation (450 cGy) and a significant decrease was found in thymic cellularity after irradiation. Defective thymopoiesis and peripheral T cell reconstitution were found in KGF (-/-) recipients of syngeneic or allogeneic bone marrow transplantation, but using KGF (-/-) mice, as a donor did not affect T cell development after transplantation.
Despite causing an early developmental block in the thymus, administration of KGF to young and old mice enhanced thymopoiesis. Exogenous KGF also accelerated thymic recovery after irradiation, cyclophosphamide and dexamethasone treatment. Finally, we found that administering KGF pre-BMT resulted in enhanced thymopoiesis and peripheral T cell numbers in middle-aged recipients of an allogeneic BMT. We conclude that KGF plays a critical role in post-natal thymic regeneration and may be useful in treating immune deficiency conditions.
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