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
N1 - Funding Information:
This study was performed through Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. The authors also wish to thank Dr. James L. McDonald for his helpful advice in writing the English manuscript.
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
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U2 - 10.1016/j.jconrel.2009.01.004
DO - 10.1016/j.jconrel.2009.01.004
M3 - Article
C2 - 19344678
AN - SCOPUS:65149089054
SN - 0168-3659
VL - 136
SP - 79
EP - 85
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -