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 language | English (US) |
|---|---|
| Pages (from-to) | 3710-3719 |
| Number of pages | 10 |
| Journal | Vaccine |
| Volume | 19 |
| Issue number | 27 |
| DOIs | |
| State | Published - Jun 14 2001 |
| Externally published | Yes |
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Keywords
- Cytotoxic T lymphocyte
- Dendritic cell
- Peptide
ASJC Scopus subject areas
- Immunology
- Microbiology
- Virology
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
Cite this
Dendritic cells generated in vivo by a chimeric hematopoietic growth factor, progenipoietin-4, demonstrate potent immunological function. / Ishioka, Glenn Y.; Fikes, John; Qin, Mingsheng; Gianfrani, Carmen; Chesnut, Robert W.; Kahn, Larry E.; Streeter, Philip; Woulfe, Susan L.; Sette, Alessandro.
In: Vaccine, Vol. 19, No. 27, 14.06.2001, p. 3710-3719.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dendritic cells generated in vivo by a chimeric hematopoietic growth factor, progenipoietin-4, demonstrate potent immunological function
AU - Ishioka, Glenn Y.
AU - Fikes, John
AU - Qin, Mingsheng
AU - Gianfrani, Carmen
AU - Chesnut, Robert W.
AU - Kahn, Larry E.
AU - Streeter, Philip
AU - Woulfe, Susan L.
AU - Sette, Alessandro
PY - 2001/6/14
Y1 - 2001/6/14
N2 - 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.
AB - 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.
KW - Cytotoxic T lymphocyte
KW - Dendritic cell
KW - Peptide
UR - http://www.scopus.com/inward/record.url?scp=0035859305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035859305&partnerID=8YFLogxK
U2 - 10.1016/S0264-410X(01)00102-5
DO - 10.1016/S0264-410X(01)00102-5
M3 - Article
C2 - 11395205
AN - SCOPUS:0035859305
VL - 19
SP - 3710
EP - 3719
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 27
ER -