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, 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-alpha (TNF-alpha) 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.
Ishioka
G Y
GY
Epimmune Inc., 5820 Nancy Ridge Dr., San Diego, CA 92121, USA. gishioka@epimmune.com
Fikes
J
J
Qin
M
M
Gianfrani
C
C
Chesnut
R W
RW
Kahn
L E
LE
Streeter
P R
PR
Woulfe
S L
SL
Sette
A
A
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D016298:Hematopoietic Cell Growth Factors; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha