Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, California, USA.
Nat Immunol. 2010 Apr;11(4):321-7. doi: 10.1038/ni.1849. Epub 2010 Feb 28.
Natural killer (NK) cells expressing inhibitory receptors that bind to self major histocompatibility complex (MHC) class I are 'licensed', or rendered functionally more responsive to stimulation, whereas 'unlicensed' NK cells lacking receptors for self MHC class I are hyporesponsive. Here we show that contrary to the licensing hypothesis, unlicensed NK cells were the main mediators of NK cell-mediated control of mouse cytomegalovirus infection in vivo. Depletion of unlicensed NK cells impaired control of viral titers, but depletion of licensed NK cells did not. The transfer of unlicensed NK cells was more protective than was the transfer of licensed NK cells. Signaling by the tyrosine phosphatase SHP-1 limited the proliferation of licensed NK cells but not that of unlicensed NK cells during infection. Thus, unlicensed NK cells are critical for protection against viral infection.
自然杀伤 (NK) 细胞表达的抑制性受体与自身主要组织相容性复合体 (MHC) Ⅰ类结合，被“许可”或使其对刺激更敏感，而缺乏自身 MHC Ⅰ类受体的“未许可”NK 细胞反应性较低。在这里，我们表明，与许可假说相反，未许可 NK 细胞是 NK 细胞介导的体内控制小鼠巨细胞病毒感染的主要介质。耗尽未许可的 NK 细胞会损害对病毒滴度的控制，但耗尽许可的 NK 细胞则不会。未许可 NK 细胞的转移比许可 NK 细胞的转移更具保护性。在感染过程中，酪氨酸磷酸酶 SHP-1 的信号转导限制了许可 NK 细胞的增殖，但不限制未许可 NK 细胞的增殖。因此，未许可的 NK 细胞对于抵抗病毒感染至关重要。
