Macrophages-releasing antigen-carrying exosomes enhance dendritic cells-mediated CD4+ T cell response (APP3P.107)

The mutual interplay of immune cells plays a critical role in the optimal adaptive immune response. Macrophages (Mϕs) and dendritic cells (DCs) are major professional antigen presenting cells (APCs) and are jointly involved in clearance of invading pathogens and maintenance of homeostasis. However, the underlying interaction mechanism remains poorly understood. In this study, we demonstrated that Mϕs, DCs, and neutrophils were predominant phagocytes that uptook apoptotic cell-associated antigens (Ags) in the spleen. Moreover, by utilizing deletion approaches with clodronate liposome (CLL) to delete Mϕ, we found that Mϕs were required for fully initiating a CD4 + T response to apoptotic cell-associated Ags. Although Mϕs themselves were inefficient to present Ags to CD4 + T cell, it was capable of transferring Ags to DCs to induce a perfect CD4 + T cell proliferation. We further discovered that the process of Ags transfer to activate CD4 + T cell was related to cell-migration and soluble factor released by Mϕs. More importantly, an exosome secretion inhibitor GW4869 could inhibit CD4 + T cell proliferation to cell-associate Ags in vitro and in vivo, which suggesting exosomes released by Mϕs acted as one of vectors to bridge DCs and Mϕs. Thus, we illustrated a new crosstalk mechanism between Mϕs and DCs, contributing to regulate the optimal adaptive immunity and maintain immune homeostasis.