| Abstract: |
Keratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNAplasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNAvaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8<sub>+</sub>. T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8<sub>+</sub> cells, as well as increased numbers of CD8 <sub>+</sub> cells producing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell-receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution. © 2009 by The American Society of Hematoloty. |
| Keywords: |
controlled study; survival rate; transplantation, homologous; nonhuman; comparative study; cd8+ t lymphocyte; cd8-positive t-lymphocytes; forkhead transcription factors; animal cell; mouse; phenotype; animals; mice; animal tissue; cell division; melanoma; tumor volume; animal experiment; animal model; allogenic bone marrow transplantation; assay; mice, inbred c57bl; survival time; t lymphocyte receptor; regulatory t lymphocyte; dna; tumor necrosis factor alpha; gamma interferon; cancer vaccines; t-lymphocytes, regulatory; thymus gland; cancer immunization; plasmid; tumor immunity; plasmids; cell fractionation; effector cell; cell count; tumor vaccine; memory cell; bone marrow transplantation; antigens, cd4; vaccines, dna; keratinocyte growth factor; graft recipient; fibroblast growth factor 7; dna immunization; immunologic memory; lymphocyte count; transplantation chimera
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