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Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. | LitMetric

AI Article Synopsis

  • Opportunistic infections after PBPC transplantation can increase morbidity and mortality, which may be linked to a lack of T-cells.
  • Researchers tested keratinocyte growth factor (KGF) in rhesus macaques to see if it could improve immune recovery after myeloablative total body irradiation and PBPC transplantation.
  • KGF-treated animals maintained better thymic structure and produced more naive T-cells than controls, indicating that KGF could enhance T-cell recovery after PBPC transplants, potentially improving patient outcomes.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1975851PMC
http://dx.doi.org/10.1182/blood-2006-12-065623DOI Listing

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