Exosomes secreted from monocyte-derived dendritic cells support in vitro naive CD4⁺ T cell survival through NF-κB 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-κB in naive CD4⁺ T cells, and NF-κB activation was significantly suppressed by anti-HLA-DR mAb or NF-κB 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-κB activation induced by interaction of HLA-DR and TCRs.