Apoptotic contraction drives target cell release by cytotoxic T cells.
Nat Immunol
; 24(9): 1434-1442, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37500886
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
/
Apoptose
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos