Induction of antigen-dependent interleukin-12 production by negatively charged liposomes encapsulating antigens.
The aim of this study was to clarify the mechanism of adjuvant action induced by negatively charged liposomes composed of phosphatidylserine (PS-liposomes). Coculture of mouse splenic adherent cells with ovalbumin (OVA)-specific Th1 clone (42-6A) cells in the presence of PS-liposomes encapsulating OVA resulted in high levels of IL-12 and IFN-gamma productions compared with those of positively charged or neutral liposomes. IL-12 and IFN-gamma productions were dose-dependent on antigens in PS-liposomes. The expression of CD40L on 42-6A cells was enhanced by treatment with PS-liposomes encapsulating OVA. IL-12 production, but not IFN-gamma, was completely inhibited by the addition of anti-CD40L mAb. These results indicate that PS-liposomes encapsulating antigens could enhance antigen-dependent IL-12 production through the interaction between CD40 on macrophage/dendritic cells and CD40L on 42-6A cells.
Yotsumoto
Satoshi
S
Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. yotumoto@ps.toyaku.ac.jp
Aramaki
Yukihiko
Y
Kakiuchi
Terutaka
T
Tsuchiya
Seishi
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D019013:CD40 Antigens / Q000008:administration & dosage* / Q000276:immunology*; D002448:Cell Adhesion; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010718:Phosphatidylserines; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D004337:Drug Carriers; D007074:Immunoglobulin G; D008081:Liposomes; D010718:Phosphatidylserines; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin