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-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. (c) 2004 Elsevier Inc. All rights reserved.