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

Glenn Y. Ishioka, John Fikes, Mingsheng Qin, Carmen Gianfrani, Robert W. Chesnut, Larry E. Kahn, Philip R. Streeter, Susan L. Woulfe, Alessandro Sette

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Recently, a dual receptor agonist for human Flt3 and G-CSF receptors, progenipoietin-4 (ProGP-4), was shown to be highly effective in expanding DC in vivo. In this study, we examined the immunological activity of ProGP-4-generated 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 lymphocyte (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 BM-DC, macrophages, or B cells at presenting PADRE, a universal helper T cell epitope, to a T cell clone. The heightened epitope 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 responses stimulated by ProGP-4 DC could be further augmented by either culturing with tumor necrosis factor-α (TNF-α) or co-loading with PADRE. Collectively, our results indicate that peptide-loaded ProGP-4-generated DC demonstrate potent antigenicity and immunogenicity for CTL, making them an attractive component of epitope-based vaccines.

Original languageEnglish (US)
Pages (from-to)3710-3719
Number of pages10
JournalVaccine
Volume19
Issue number27
DOIs
StatePublished - Jun 14 2001

Keywords

  • Cytotoxic T lymphocyte
  • Dendritic cell
  • Peptide

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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