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Phosphatidylserine-positive extracellular vesicles boost effector CD8+ T cell responses during viral infection.
Rausch, Lisa; Flaskamp, Lavinia; Ashokkumar, Ashretha; Trefzer, Anne; Ried, Christine; Buchholz, Veit R; Obst, Reinhard; Straub, Tobias; Brocker, Thomas; Kranich, Jan.
Afiliación
  • Rausch L; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Flaskamp L; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Ashokkumar A; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Trefzer A; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Ried C; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Buchholz VR; Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany.
  • Obst R; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Straub T; Core Facility Bioinformatics, Faculty of Medicine, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Brocker T; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
  • Kranich J; Faculty of Medicine, Institute for Immunology, Biomedical Center, Ludwig Maximilian University of Munich, 82152 Martinsried-Planegg, Germany.
Proc Natl Acad Sci U S A ; 120(16): e2210047120, 2023 04 18.
Article en En | MEDLINE | ID: mdl-37040405
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Virosis / Vesículas Extracelulares Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2023 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Virosis / Vesículas Extracelulares Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2023 Tipo del documento: Article País de afiliación: Alemania