Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes
In: The Journal of Immunology, Jg. 197 (2016-09-15), S. 2473-2484
Online
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Zugriff:
CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes. CGs are refilled with granzyme B at the late endosome stage and polarize to subsequent synapses formed between the CTL and new target cells. Importantly, inhibiting CG endocytosis in CTLs results in a significant reduction of their cytotoxic activity. Thus, our data demonstrate that continuous endocytosis of CG membrane proteins is a prerequisite for efficient serial killing of CTLs and identify key events in this process.
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Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes
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Autor/in / Beteiligte Person: | Cordat, Emmanuelle ; Krause, Elmar ; Rettig, Jens ; Chang, Hsin-Fang ; Halimani, Mahantappa ; Bzeih, Hawraa ; Schirra, Claudia ; Chitirala, Praneeth ; Pattu, Varsha |
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Zeitschrift: | The Journal of Immunology, Jg. 197 (2016-09-15), S. 2473-2484 |
Veröffentlichung: | The American Association of Immunologists, 2016 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.1600828 |
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