Dendritic cells (DCs) are known to secrete exosomes that transfer membrane proteins, like major histocompatibility complex class II, to other DCs. Intercellular transfer of membrane proteins is also observed during cognate interactions between DCs and CD4⁺ T cells. The acquired proteins are functional and play a role in regulation of immune responses. How membrane protein transfer is achieved and regulated is unclear. Here we show that T cells can recruit major histocompatibility complex class II–containing DC exosomes secreted in the extracellular milieu during cognate DC–T-cell interactions. Recruitment of these exosomes required T-cell activation and was dependent on leukocyte function–associated antigen-1 (LFA-1) rather than on T-cell receptor specificity. Indeed, inducing a high-affinity state of LFA-1 on resting T cells was sufficient to provoke exosome binding. These results imply that DC exosomes secreted in the extracellular milieu during cognate T-cell–DC interactions are targeted to T cells activated in that microenvironment.

In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16⁺, CD1c⁺, and BDCA-3⁺ myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8⁺ T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c⁺ and BDCA3⁺ mDCs, pDCs induce potent Ag-specific CD4⁺ and CD8⁺ T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4⁺ and CD8⁺ T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3⁺ mDCs. These findings, and the fact that pDCs outnumber BDCA3⁺ mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8⁺ T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.