Phosphatidylserine-positive extracellular vesicles boost effector CD8+ T cell responses during viral infection

Proc Natl Acad Sci U S A. 2023 Apr 18;120(16):e2210047120. doi: 10.1073/pnas.2210047120. Epub 2023 Apr 11.


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.

Keywords: CD8 T cells; LCMV; exosomes; extracellular vesicles; phosphatidylserine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Extracellular Vesicles* / metabolism
  • Humans
  • Phosphatidylserines / metabolism
  • Virus Diseases* / metabolism


  • Phosphatidylserines