Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4+ T cell survival through NF-(kappa)B activation.
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.
Matsumoto
Kotaro
K
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Morisaki
Takashi
T
Kuroki
Hideo
H
Kubo
Makoto
M
Onishi
Hideya
H
Nakamura
Katsuya
K
Nakahara
Chihiro
C
Kuga
Hirotaka
H
Baba
Eishi
E
Nakamura
Masafumi
M
Hirata
Kazuho
K
Tanaka
Masao
M
Katano
Mitsuo
M
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
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