title: Oligomannose-coated liposomes efficiently induce human T-cell leukemia virus-1-specific cytotoxic T lymphocytes without adjuvant.
abstract: Human T-cell leukemia virus-1 (HTLV-1) causes adult T-cell leukemia/lymphoma, which is an aggressive peripheral T-cell neoplasm. Insufficient T-cell response to HTLV-1 is a potential risk factor in adult T-cell leukemia/lymphoma. Efficient induction of antigen-specific cytotoxic T lymphocytes is important for immunological suppression of virus-infected cell proliferation and oncogenesis, but efficient induction of antigen-specific cytotoxic T lymphocytes has evaded strategies utilizing poorly immunogenic free synthetic peptides. Here, we examined the efficient induction of an HTLV-1-specific CD8+ T-cell response by oligomannose-coated liposomes (OMLs) encapsulating the human leukocyte antigen (HLA)-A*0201-restricted HTLV-1 Tax-epitope (OML/Tax). Immunization of HLA-A*0201 transgenic mice with OML/Tax induced an HTLV-1-specific gamma-interferon reaction, whereas immunization with epitope peptide alone induced no reaction. Upon exposure of dendritic cells to OML/Tax, the levels of CD86, major histocompatibility complex class I, HLA-A02 and major histocompatibility complex class II expression were increased. In addition, our results showed that HTLV-1-specific CD8+ T cells can be efficiently induced by OML/Tax from HTLV-1 carriers compared with epitope peptide alone, and these HTLV-1-specific CD8+ T cells were able to lyse cells presenting the peptide. These results suggest that OML/Tax is capable of inducing antigen-specific cellular immune responses without adjuvants and may be useful as an effective vaccine carrier for prophylaxis in tumors and infectious diseases by substituting the epitope peptide.
authors.affiliation: Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. kozako@fukuoka-u.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kozako
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Satoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshimitsu
authors.forename: Yohann
authors.initials: Y
authors.lastname: White
authors.forename: François
authors.initials: F
authors.lastname: Lemonnier
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimeno
authors.forename: Shinji
authors.initials: S
authors.lastname: Soeda
authors.forename: Naomichi
authors.initials: N
authors.lastname: Arima
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D015490:HTLV-I Infections / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology; D008081:Liposomes / Q000494:pharmacology*; D051379:Mice; D009844:Oligosaccharides / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
chemical_list: D008081:Liposomes; D009844:Oligosaccharides; C028569:oligomannoside