Enhancement of IFN-gamma production for Th1-cell therapy using negatively charged liposomes containing phosphatidylserine.
We have developed an efficient method of interferon-gamma (IFN-gamma) induction for Th1-cell therapy. OVA (ovalbumin)-specific Th1 clone 42-6A cells cocultured with antigen presenting cells (APCs) from spleen resulted in high levels of OVA-specific IFN-gamma production by the treatment of phosphatidylserine (PS), but not phosphatidic acid (PA), liposomes-encapsulated OVA (OVA-liposomes). The IFN-gamma production was increased in a manner dependent on the PS content of the liposomes and inhibited by the addition of annexin V, a PS binding protein. Furthermore, coadministration of Th1 cells plus OVA-liposomes in mice strikingly enhanced IFN-gamma levels in serum and in spleen cells compared with that of Th1 cells plus OVA. In addition, serum levels of IL-12 p70 increased and ongoing OVA-specific IgE immune response was dramatically attenuated. These results first suggest that antigen delivery using negatively charged liposomes containing PS is very useful for the enhancement of IFN-gamma production in Th1-cell therapy.
Yotsumoto
Satoshi
S
Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Kakiuchi
Terutaka
T
Aramaki
Yukihiko
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D007073:Immunoglobulin E / Q000097:blood; D007155:Immunologic Factors / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D007155:Immunologic Factors; D008081:Liposomes; D010718:Phosphatidylserines; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin