Taniguchi Ruth T, Guzior Dustin, Kumar Vinay
University of Chicago Department of Pathology, Committee on Immunology, Chicago, IL 60637, USA.
Blood. 2007 Sep 15;110(6):2020-3. doi: 10.1182/blood-2007-02-076927. Epub 2007 May 30.
2B4 (CD244) and its ligand, CD48, are expressed on all natural killer (NK) cells. In studies using 2B4-deficient, CD48-deficient, or wild-type NK cells with blocking antibodies, we found that in the absence of 2B4-CD48 interactions, activated murine NK cells kill each other. We also show that NK-NK fratricide in the absence of 2B4-CD48 interaction is dependent on perforin both in vitro and in vivo. 2B4 has been reported to have activating, costimulatory, and inhibitory functions on murine NK cells. 2B4-mediated inhibition of NK-cell fratricide explains some of the paradoxes of 2B4 function reported in studies of murine NK cells. We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal.
2B4（CD244）及其配体CD48在所有自然杀伤（NK）细胞上均有表达。在使用2B4缺陷型、CD48缺陷型或野生型NK细胞与阻断抗体的研究中，我们发现，在缺乏2B4 - CD48相互作用的情况下，活化的小鼠NK细胞会相互杀伤。我们还表明，在缺乏2B4 - CD48相互作用时，NK细胞间的自相残杀在体外和体内均依赖穿孔素。据报道，2B4对小鼠NK细胞具有激活、共刺激和抑制功能。2B4介导的对NK细胞自相残杀的抑制解释了在小鼠NK细胞研究中报道的2B4功能的一些矛盾之处。我们表明，在缺乏2B4信号时，活化的NK细胞由于自相残杀而具有缺陷的细胞毒性和增殖能力，而非由于缺乏2B4依赖性激活信号。
