A minimal human immunostimulatory CpG motif that potently induces IFN-gamma and IFN-alpha production.
Eur J Immunol
; 33(8): 2114-22, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12884285
ABSTRACT
Recent reports have shown that immunostimulatory sequences (ISS) containing CpG motifs have minimal length requirements (>/=12 bases) for the exertion of immune-enhancing function upon mammalian cells. Herein we demonstrate that short ISS (5-7 bases), which exhibit no activity on their own, induce IFN-gamma and IFN-alpha secretion from human peripheral blood mononuclear cells when adsorbed to the surface of cationic poly(D,L-lactide-co-glycolide) microparticles (cPLGA). Utilizing this technique, we discovered a minimal ISS sequence for induction of IFN-gamma and IFN-alpha from human cells 5'-TCGXX-3'. These short ISS/cPLGA formulations targeted PDC in similar fashion to longer ISS ODN, the activity of which does not require (but is enhanced by) cPLGA. PDC stimulated with short ISS/cPLGA responded with enhanced uptake of ISS and elevated production of cytokines, including IFN-alpha. However, ISS-responsive B cells did not respond to short ISS/cPLGA, underlining the plasmacytoid dendritic cell selectivity of this formulation. These results describe a novel technique for formulating active, but very short, ISS oligodeoxynucleotide that allows for the dissection and characterization of minimal immunostimulatory CpG motifs.
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Base de dados:
MEDLINE
Assunto principal:
Oligodesoxirribonucleotídeos
/
Adjuvantes Imunológicos
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Interferon gama
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Interferon-alfa
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos