Phosphatidylserine-positive extracellular vesicles boost effector CD8 <sup>+</sup> T cell responses during viral infection
Lisa Rausch, Lavinia Flaskamp, Ashretha Ashokkumar, Anne Trefzer, Christine Ried, Veit R. Buchholz, Reinhard Obst, Tobias Straub, Thomas Brocker, Jan Kranich
Abstract
CD8 + T cells are crucial for the clearance of viral infections. During the acute phase, proinflammatory conditions increase the amount of circulating phosphatidylserine + (PS) extracellular vesicles (EVs). These EVs interact especially with CD8 + T cells; however, it remains unclear whether they can actively modulate CD8 + T cell responses. In this study, we have developed a method to analyze cell-bound PS + EVs and their target cells in vivo. We show that EV + cell abundance increases during viral infection and that EVs preferentially bind to activated, but not naive, CD8 + T cells. Superresolution imaging revealed that PS + EVs attach to clusters of CD8 molecules on the T cell surface. Furthermore, EV-binding induces antigen (Ag)-specific TCR signaling and increased nuclear translocation of the transcription factor Nuclear factor of activated T-cells (NFATc1) in vivo. EV-decorated but not EV-free CD8 + T cells are enriched for gene signatures associated with T-cell receptor signaling, early effector differentiation, and proliferation. Our data thus demonstrate that PS + EVs provide Ag-specific adjuvant effects to activated CD8 + T cells in vivo.