Enhanced in vivo growth of lymphoma tumors in the absence of the NK-activating receptor NKp46/NCR1.
J Immunol
; 182(4): 2221-30, 2009 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-19201876
ABSTRACT
The in vitro elimination of virus-infected and tumor cells by NK cells is regulated by a balance between signals conveyed via specific inhibitory and activating receptors. Whether NK cells and specifically the NK-activating receptor NKp46 (NCR1 in mice) are directly involved in tumor eradication in vivo is still largely unknown. Since the NKp46/NCR1 tumor ligands have not been identified yet, we use a screening technique to identify functional ligands for NKp46/NCR1 which is based on a cell reporter assay and discover a NCR1 ligand in the PD1.6 lymphoma line. To study whether NKp46/NCR1 is important for the eradication of PD1.6 lymphoma in vivo, we used the Ncr1 knockout Ncr1(gfp/gfp) mice generated by our group. Strikingly, all Ncr1 knockout mice developed growing PD1.6 tumors, whereas initial tumor growth was observed in the wild-type mice and tumors were completely rejected as time progressed. The growth of other lymphoma cell lines such as B10 and EL4 was equivalent between the Ncr1 knockout and wild-type mice. Finally, we show that PD1.6 lymphoma cells are less killed both in vitro and in vivo in the absence of NKp46/NCR1. Our results therefore reveal a crucial role for NKp46/NCR1 in the in vivo eradication of some lymphoma cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Antígenos Ly
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Citotoxicidade Imunológica
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Receptor 1 Desencadeador da Citotoxicidade Natural
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Linfoma
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article