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Blood, 1 July 2007, Vol. 110, No. 1, pp. 441-449.
Prepublished online as a Blood First Edition Paper on March 20, 2007; DOI 10.1182/blood-2006-12-065623.
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Submitted December 29, 2006
Accepted March 15, 2007
Keratinocyte growth factor augments immune
reconstitution after autologous hematopoietic progenitor
cell transplantation in rhesus macaques
Ruth Seggewiss, Karin Lore, F. Javier Guenaga, Stefania Pittaluga, Joseph Mattapallil, Catherine K Chow, Richard A Koup, Kevin Camphausen, Martha C Nason, Martin Meier-Schellersheim, Robert E Donahue, Bruce R Blazar, Cynthia E Dunbar, and Daniel C Douek*
Hematology Branch, NHLBI, NIH/DHHS, Bethesda, MD, United States
Immunology Laboratory, VRC/NIAID/NIH/DHHS, Bethesda, MD, United States
Human Immunology Section, VRC/NIAID/NIH/DHHS, Bethesda, MD, United States
Hematopathology Section, NCI, NIH/DHHS, Bethesda, MD, United States
ImmunoTechnology Section, VRC/NIAID/NIH/DHHS, Bethesda, MD, United States
Diagnostic Radiology, Clinical Center, NIH/DHHS, Bethesda, MD, United States
Radiation Oncology Branch, NCI, NIH/DHHS, Bethesda, MD, United States
Biostatistics Research Branch, NIAID/NIH/DHHS, Bethesda, MD, United States
Laboratory of Immunology, NIAD/NIH/DHHS, Bethesda, MD, United States
Cancer Center & Dept of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, MN, United States
* Corresponding author; email: ddouek{at}nih.gov.
Opportunistic infections contribute to morbidity and mortality after peripheral blood progenitor cell (PBPC) transplantation and are related to a deficient T cell compartment. Accelerated T cell reconstitution may therefore be clinically beneficent. Keratinocyte growth factor (KGF) has been shown to protect thymic epithelial cells in mice. Here, we evaluated immune reconstitution after autologous CD34+ PBPC transplantation in rhesus macaques conditioned with myeloablative total body irradiation (TBI) in the absence or presence of single pre-TBI or repeated peri-transplant KGF administration. All KGF-treated animals exhibited a well-preserved thymic architecture 12 months post-graft. In contrast, thymic atrophy was observed in the majority of animals in the control group. The KGF-treated animals showed higher frequencies of naive T cells in lymph nodes post transplantation compared to the control animals. The animals given repeated doses of KGF showed the highest levels of TRECs and the lowest frequencies of Ki67+ T cells, which suggest increased thymic-dependent reconstitution in these animals. Of note, the humoral response to a T cell dependent neo-antigen was significantly higher in the KGF-treated animals compared to the control animals. Thus, our findings suggest that KGF may be a useful adjuvant therapy to augment T cell reconstitution after human PBPC transplantation.
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