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Tumour-experienced T cells promote NK cell activity through trogocytosis of NKG2D and NKp46 ligands.


ABSTRACT: Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)-gamma secretion on engagement of the natural-killer group (NKG)2D receptor or members of the natural cytotoxicity receptor (NCR) family, such as NKp46, by ligands expressed on tumour cells. However, it remains unknown whether T cells can regulate NK cell-mediated anti-tumour responses. Here, we investigated the early events occurring during T cell-tumour cell interactions, and their impact on NK cell functions. We observed that on co-culture with some melanomas, activated CD4(+) T cells promoted degranulation, and NKG2D- and NKp46-dependent IFN-gamma secretion by NK cells, probably owing to the capture of NKG2D and NKp46 ligands from the tumour-cell surface (trogocytosis). This effect was observed in CD4(+), CD8(+) and resting T cells, which showed substantial amounts of cell surface major histocompatibility complex class I chain-related protein A on co-culture with tumour cells. Our findings identify a new, so far, unrecognized mechanism by which effector T cells support NK cell function through the capture of specific tumour ligands with profound implications at the crossroad of innate and adaptive immunity.

SUBMITTER: Domaica CI 

PROVIDER: S-EPMC2726665 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Tumour-experienced T cells promote NK cell activity through trogocytosis of NKG2D and NKp46 ligands.

Domaica Carolina I CI   Fuertes Mercedes B MB   Rossi Lucas E LE   Girart María V MV   Avila Damián E DE   Rabinovich Gabriel A GA   Zwirner Norberto W NW  

EMBO reports 20090605 8


Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)-gamma secretion on engagement of the natural-killer group (NKG)2D receptor or members of the natural cytotoxicity receptor (NCR) family, such as NKp46, by ligands expressed on tumour cells. However, it remains unknown whether T cells can regulate NK cell-mediated anti-tumour responses. Here, we investigated the early events occurring during T cell-tumour cell interactions, and their impact on NK cell functions. We observed that  ...[more]

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