Phosphatidylserine-positive extracellular vesicles boost effector CD8+ T cell responses during viral infection
PNAS article from the Brocker lab with collaboration from the Buchholz lab
18.04.2023
Lisa Rausch, Lavinia Flaskamp, Ashretha Ashokkumar, Anne Trefzer, Christine Ried, Veit R Buchholz, Reinhard Obst, Tobias Straub, Thomas Brocker, Jan Kranich (2023 Apr 18) Phosphatidylserine-positive extracellular vesicles boost effector CD8+ T cell responses during viral infection. PNAS 120(16):e2210047120. doi: 10.1073/pnas.2210047120 (Projects B03, B15, Z02)
Abstract cited from the paper:
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.
