Tumour-experienced T cells promote NK cell activity through trogocytosis of NKG2D and NKp46 ligands.
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.
Domaica
Carolina I
CI
Institute of Biology and Experimental Medicine (IBYME), National Research Council (CONICET), Ciudad de Buenos Aires, Argentina.
Fuertes
Mercedes B
MB
Rossi
Lucas E
LE
Girart
María V
MV
Avila
Damián E
DE
Rabinovich
Gabriel A
GA
Zwirner
Norberto W
NW
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D018613:Microscopy, Confocal; D008934:Mitogens / Q000494:pharmacology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D007376:Interleukin-2; D008934:Mitogens; C112260:NCR1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D010835:Phytohemagglutinins; D007371:Interferon-gamma