title: In Vivo Inverse Correlation in the Activation of Natural Killer T Cells Through Dual-Signal Stimulation via a Combination of α-Galactosylceramide-Loaded Liposomes and Interleukin-12.
abstract: Alpha-galactosylceramide (GC) represents a potentially new class of adjuvant because GC strongly induces interferon (IFN) gamma production from natural killer T (NKT) cells, leading to the induction of strong antitumor immunity. Interleukin (IL)-12 is another stimulating signal that induces IFN-γ production by NKT cells. We report herein on an investigation of the effect of recombinant IL-12 on NKT cell activation, when used in combination with GC-loaded octaarginine modified liposomes (GC-Lip). IFN-γ production from splenocytes simulated with GC-Lip was dose dependently enhanced in the presence of IL-12 in vitro. In contrast, IFN-γ production in vivo was enhanced at a low dose of IL-12. Enhanced IFN-γ production was observed in the case of low doses (0.5 μg and 2.5 μg) of GC-Lip but not a high dose (5 μg), that is, the IL-12 combination enhanced NKT cell activation at a 10-fold lower GC dose. The use of the above combination also enhanced the expansion of the NKT cell population. These findings indicate that in vivo IFN-γ production is inversely correlated with the dose of IL-12 during dual signal stimulation of NKT cells via both GC-Lip and IL-12, indicating that the dose of GC-Lip can be reduced without weakening NKT cell activation.
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, 060-0812, Japan.
authors: Heba
authors: H
authors: Abdelmegeed
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, 060-0812, Japan.
authors: Takashi
authors: T
authors: Nakamura
authors: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo, 060-0812, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.
authors: Hideyoshi
authors: H
authors: Harashima
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects*; D009842:Oligopeptides; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D005699:Galactosylceramides; D008081:Liposomes; D009842:Oligopeptides; D014612:Vaccines; C493154:alpha-galactosylceramide; C448619:octaarginine; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: liposomes; nanoparticles; vaccine adjuvants; vaccine delivery