Liposomes with differential lipid components exert differential adjuvanticity in antigen-liposome conjugates via differential recognition by macrophages.
We previously reported that liposomes having differential lipid components displayed differential adjuvant effects when antigen was coupled with liposomes via glutaraldehyde. In the present study, antigen-liposome conjugates prepared using liposomes having differential lipid components were added to the macrophage culture, and phagocytosis and the antigen digest of liposome-coupled antigen by macrophages were then investigated. Antigen presentation by macrophages to an antigen-specific T-cell clone was further investigated using the same conjugates. Antigen-liposome conjugates which induced higher levels of antibody production in vivo were recognized more often, and the liposome-coupled antigen was digested to a greater degree by macrophages than antigen-liposome conjugates which induced lower levels of antibody production. These results correlated closely with those regarding antigen presentation by macrophages; when antigen was coupled to liposomes showing higher adjuvant effect, macrophages cocultured with antigen-liposome conjugates activated antigen-specific T-cells at a higher degree. The concentration of OVA in the macrophage culture added as antigen-liposome conjugates was approximately 32 microg/mL. However, the extent of T-cell activation was almost equal to that when 800 microg/mL of soluble OVA was added to the culture. The results of the present study demonstrated that the adjuvant activity of liposomes observed primary in vivo correlated closely with the recognition of antigen-liposome conjugates and antigen presentation of liposome-coupled antigen by macrophages, suggesting that the adjuvant effects of liposomes are exerted at the beginning of the immune response, i.e., recognition of antigen by antigen-presenting cells.
Tanaka
Yuriko
Y
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Kasai
Michiyuki
M
Taneichi
Maiko
M
Naito
Seishiro
S
Kato
Hiroshi
H
Mori
Masahito
M
Nishida
Mitsuhiro
M
Maekawa
Naoya
N
Yamamura
Hiroyuki
H
Komuro
Katsutoshi
K
Uchida
Tetsuya
T
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000032:analysis; D000938:Antigen-Presenting Cells / Q000187:drug effects; D000941:Antigens / Q000737:chemistry*; D002999:Clone Cells; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D005976:Glutaral / Q000737:chemistry; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000737:chemistry; D010587:Phagocytosis / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000941:Antigens; D007074:Immunoglobulin G; D008055:Lipids; D008081:Liposomes; D010047:Ovalbumin; D005976:Glutaral