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Apoptotic contraction drives target cell release by cytotoxic T cells.
Sanchez, Elisa E; Tello-Lafoz, Maria; Guo, Aixuan J; de Jesus, Miguel; Elbanna, Yassmin A; Winer, Benjamin Y; Budhu, Sadna; Chan, Eric; Rosiek, Eric; Kondo, Taisuke; DuSold, Justyn; Taylor, Naomi; Altan-Bonnet, Gregoire; Olson, Michael F; Huse, Morgan.
Afiliación
  • Sanchez EE; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Tello-Lafoz M; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Guo AJ; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • de Jesus M; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Elbanna YA; Louis V. Gerstner Jr Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Winer BY; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Budhu S; Louis V. Gerstner Jr Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Chan E; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Rosiek E; Department of Pharmacology, Weill-Cornell Medical College, New York, NY, USA.
  • Kondo T; Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • DuSold J; Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Taylor N; Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Altan-Bonnet G; Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Olson MF; Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Huse M; Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Nat Immunol ; 24(9): 1434-1442, 2023 09.
Article en En | MEDLINE | ID: mdl-37500886
Cytotoxic T lymphocytes (CTLs) fight intracellular pathogens and cancer by identifying and destroying infected or transformed target cells1. To kill, CTLs form a specialized cytotoxic immune synapse (IS) with a target of interest and then release toxic perforin and granzymes into the interface to elicit programmed cell death2-5. The IS then dissolves, enabling CTLs to search for additional prey and professional phagocytes to clear the corpse6. While the mechanisms governing IS assembly have been studied extensively, far less is known about target cell release. Here, we applied time-lapse imaging to explore the basis for IS dissolution and found that it occurred concomitantly with the cytoskeletal contraction of apoptotic targets. Genetic and pharmacological perturbation of this contraction response indicated that it was both necessary and sufficient for CTL dissociation. We also found that mechanical amplification of apoptotic contractility promoted faster CTL detachment and serial killing. Collectively, these results establish a biophysical basis for IS dissolution and highlight the importance of mechanosensory feedback in the regulation of cell-cell interactions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Apoptosis Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Citotóxicos / Apoptosis Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos