期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 4, 页码 2221-2230出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0801878
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资金
- US-Israel Bi-national Science Foundation
- Israeli Cancer Research Foundation
- Israeli Science Foundation
- European Consortium ( [MRTN-CT-2005, I-SCH-CT-2005-518178]
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 Ncrl knockout Ncr1(gfp/gfp) mice generated by our group. Strikingly, all Ncrl 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 Ncrl 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. The Journal of Immunology, 2009, 182: 2221-2230.
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