Dendritic cells generated in vivo by a chimeric hematopoietic growth factor, progenipoietin-4, demonstrate potent immunological function

Recently, a dual receptor agonist for human Flt3 and G-CSF receptors, proge nipoietin-4, (ProGP-4), was shown to be highly effective in expanding DC in vivo. Tn this study, we examined the immunological activity of ProGP-4-gen erated dendritic cell (DC) in an HLA-A2.1 transgenic mouse system. ProGP-4- DC were found to be approximately equivalent in presenting a cytotoxic T ly mphocyte (CTL) peptide to a CTL line in vitro compared with bone marrow (BM )-derived DC and > 20-fold more efficient than macrophages or B cells, and > 100-fold better than PM-DC, macrophages, or B cells at presenting PADRE, a universal helper T cell epitope, to a T cell clone. The heightened epitop e presentation by ProGP-4 DC was paralleled in vivo inasmuch as a > 6-fold increase in CTL induction was observed compared with other APC populations following ex vivo loading with peptide. The in vitro and in vivo CTL respon ses stimulated by ProGP-4 DC could be further augmented by either culturing with tumor necrosis factor-alpha (TNF-alpha) or co-loading with PADRE. Col lectively, our results indicate that peptide-loaded ProGP-4-generated DC de monstrate potent antigenicity and immunogenicity for CTL, making them an at tractive component of epitope-based vaccines. (C) 2001 Elsevier Science Ltd . All rights reserved.