title: Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4+ T cell survival through NF-(kappa)B activation.
abstract: We investigated the effect of exosomes secreted from human monocyte-derived dendritic cells (Mo-DCs), which are generated from PBMCs in response to treatment with GM-CSF and IL-4, on naive CD4+ T cell survival in vitro. Exosomes isolated from culture supernatants of Mo-DCs (>90% purity) were purified with anti-HLA-DP, -DQ, -DR-coated paramagnetic beads. Purified exosomes prolonged the survival of naive CD4+ T cells (>98% purity) in vitro. Treatment with neutralizing mAb against HLA-DR significantly decreased the supportive effect of purified exosomes on CD4+ T cell survival. Exosomes increased nuclear translocation of NF-(kappa)B in naive CD4+ T cells, and NF-(kappa)B activation was significantly suppressed by anti-HLA-DR mAb or NF-(kappa)B inhibitor pyrrolidine dithiocarbamate (PDTC). In addition, PDTC inhibited the effect of exosomes on naive CD4+ T cell survival. Thus, exosomes secreted by Mo-DCs appear to support naive CD4+ T cell survival via NF-(kappa)B activation induced by interaction of HLA-DR and TCRs.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Kuroki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakamura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Nakahara
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kuga
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kazuho
authors.initials: K
authors.lastname: Hirata
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D005089:Exocytosis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D008854:Microscopy, Electron; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell