Antigen-presenting cell–derived exosomes influence T cell activation by carrying molecular cues that either directly stimulate T cells or reshape the antigen-presenting landscape. Work by Clotilde Théry at Institut Curie and Laurence Zitvogel at Institut Gustave Roussy established foundational concepts showing that vesicles released from dendritic cells and B cells harbour peptide–MHC complexes and accessory molecules, enabling intercellular antigen transfer and modulation of adaptive responses. The functional outcome depends on the exosome cargo and the immunological context.
Mechanisms
Exosomes display surface peptide–MHC complexes and co-stimulatory molecules such as CD80/CD86 and adhesion proteins that can engage T cell receptors and synapse components. These vesicles may activate T cells directly by presenting antigen in a multivalent form or indirectly by fusing with or being internalized by other antigen-presenting cells, which then cross-present antigens to T cells. Exosomes also shuttle regulatory cargos including microRNAs, heat-shock proteins, and enzymes that alter signalling pathways within recipient cells. Maturation state of the parent APC and local cytokines influence exosome composition: inflammatory stimuli promote vesicles enriched for immunostimulatory ligands, whereas steady-state or tolerogenic APCs release exosomes biased toward immune regulation.
Relevance and consequences
Functionally, APC-derived exosomes can amplify immune responses, promote cytotoxic T lymphocyte priming in anti-tumor and anti-viral settings, or contribute to peripheral tolerance by inducing anergy or regulatory T cell pathways. In tumour microenvironments, exosome-mediated antigen dissemination can either support anti-tumour immunity or be subverted to suppress T cell function, depending on payload and co-existing checkpoints. In tissues such as the placenta or mucosal surfaces, exosome-driven tolerance helps maintain fetal-maternal harmony and limit harmful inflammation, demonstrating important cultural and territorial nuances in how immune modulation manifests across physiological sites.
Clinically, these properties underpin experimental exosome-based vaccines and immunotherapies, as well as concerns that pathogen- or tumour-derived exosomes may spread immune-evasive signals. Evidence synthesized by Théry Institut Curie and Zitvogel Institut Gustave Roussy supports the view that targeting exosome biogenesis or modifying vesicle cargo represents a strategic lever to steer T cell activation toward protective immunity or controlled tolerance. Precise therapeutic translation requires careful control of vesicle composition and an understanding of local tissue environments.