title: Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques.
abstract: 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.
authors: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors: Ruth
authors: R
authors: Seggewiss
authors: Karin
authors: K
authors: Loré
authors: F Javier
authors: FJ
authors: Guenaga
authors: Stefania
authors: S
authors: Pittaluga
authors: Joseph
authors: J
authors: Mattapallil
authors: Catherine K
authors: CK
authors: Chow
authors: Richard A
authors: RA
authors: Koup
authors: Kevin
authors: K
authors: Camphausen
authors: Martha C
authors: MC
authors: Nason
authors: Martin
authors: M
authors: Meier-Schellersheim
authors: Robert E
authors: RE
authors: Donahue
authors: Bruce R
authors: BR
authors: Blazar
authors: Cynthia E
authors: CE
authors: Dunbar
authors: Daniel C
authors: DC
authors: Douek
mesh_terms: 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
chemical_list: D051523:Fibroblast Growth Factor 7