Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques.
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 in the absence or presence of single pretotal body irradiation or repeated peritransplant KGF administration. All KGF-treated animals exhibited a well-preserved thymic architecture 12 months after 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 after transplantation compared with the control animals. The animals given repeated doses of KGF showed the highest levels of T-cell receptor excision circles (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 with the control animals. Thus, our findings suggest that KGF may be a useful adjuvant therapy to augment T-cell reconstitution after human PBPC transplantation.
Seggewiss
Ruth
R
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Loré
Karin
K
Guenaga
F Javier
FJ
Pittaluga
Stefania
S
Mattapallil
Joseph
J
Chow
Catherine K
CK
Koup
Richard A
RA
Camphausen
Kevin
K
Nason
Martha C
MC
Meier-Schellersheim
Martin
M
Donahue
Robert E
RE
Blazar
Bruce R
BR
Dunbar
Cynthia E
CE
Douek
Daniel C
DC
D000818:Animals; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects*; D007107:Immune System / Q000166:cytology / Q000502:physiology; D008253:Macaca mulatta; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012038:Regeneration / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous
D051523:Fibroblast Growth Factor 7