TY - JOUR
T1 - Enhanced antigen presentation and CTL activity by transduction of mature rather than immature dendritic cells with octaarginine-modified liposomes
AU - Homhuan, Atthachai
AU - Kogure, Kentaro
AU - Nakamura, Takashi
AU - Shastri, Nilabh
AU - Harashima, Hideyoshi
PY - 2009/5/21
Y1 - 2009/5/21
N2 - To improve uptake and cross-presentation of exogenous antigens (Ag) by dendritic cells (DCs), octaarginine-modified liposomes (R8-Lip) were used as a novel strategy for protein-Ag transduction. Immature DCs endocytose macromolecules efficiently. While mature DCs lose their ability to capture Ag, but have an increased capacity for T-cell activation. Thus Ag-transduction has been performed mostly in immature DCs. In the present study, R8-Lip were efficiently taken up by both immature and mature DCs. DCs transduced after maturation were highly efficient at cross-presentation of Ag and induced higher cytotoxic T-lymphocytes (CTL) activity than were DCs transduced before maturation. The mechanism of Ag presentation involved the escape of R8-Lip from endosomes to cytosol, which require the acidic environment. The Ag released was then processed by a proteasome-dependent pathway. This novel transduction approach is clinically applicable, easy to perform, and has more practical advantages than current protein transduction methods.
AB - To improve uptake and cross-presentation of exogenous antigens (Ag) by dendritic cells (DCs), octaarginine-modified liposomes (R8-Lip) were used as a novel strategy for protein-Ag transduction. Immature DCs endocytose macromolecules efficiently. While mature DCs lose their ability to capture Ag, but have an increased capacity for T-cell activation. Thus Ag-transduction has been performed mostly in immature DCs. In the present study, R8-Lip were efficiently taken up by both immature and mature DCs. DCs transduced after maturation were highly efficient at cross-presentation of Ag and induced higher cytotoxic T-lymphocytes (CTL) activity than were DCs transduced before maturation. The mechanism of Ag presentation involved the escape of R8-Lip from endosomes to cytosol, which require the acidic environment. The Ag released was then processed by a proteasome-dependent pathway. This novel transduction approach is clinically applicable, easy to perform, and has more practical advantages than current protein transduction methods.
KW - Antigen presentation
KW - Cytotoxic T lymphocytes
KW - Dendritic cells
KW - Octaarginine-modified liposomes
KW - Protein transduction
UR - http://www.scopus.com/inward/record.url?scp=65149089054&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65149089054&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.01.004
DO - 10.1016/j.jconrel.2009.01.004
M3 - Article
C2 - 19344678
AN - SCOPUS:65149089054
VL - 136
SP - 79
EP - 85
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -