Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Blood. 2010 Jun 3;115(22):4377-83. doi: 10.1182/blood-2009-09-245464. Epub 2010 Feb 4.
Natural killer (NK) cells were identified by their ability to kill target cells without previous sensitization. However, without an antecedent "arming" event, NK cells can recognize, but are not equipped to kill, target cells. How NK cells become armed in vivo in healthy hosts is unclear. Because latent herpesviruses are highly prevalent and alter multiple aspects of host immunity, we hypothesized that latent herpesvirus infection would arm NK cells. Here we show that NK cells from mice latently infected with Murid herpesvirus 4 (MuHV-4) were armed as evidenced by increased granzyme B protein expression, cytotoxicity, and interferon-gamma production. NK-cell arming occurred rapidly in the latently infected host and did not require acute viral infection. Furthermore, NK cells armed by latent infection protected the host against a lethal lymphoma challenge. Thus, the immune environment created by latent herpesvirus infection provides a mechanism whereby host NK-cell function is enhanced in vivo.
自然杀伤 (NK) 细胞因其无需预先致敏即可杀死靶细胞的能力而被识别。然而，在没有先前的“武装”事件的情况下，NK 细胞可以识别靶细胞，但不具备杀死靶细胞的能力。NK 细胞在健康宿主中如何在体内被武装尚不清楚。由于潜伏性疱疹病毒广泛存在，并改变宿主免疫的多个方面，我们假设潜伏性疱疹病毒感染会武装 NK 细胞。在这里，我们表明，潜伏感染 Murid 疱疹病毒 4 (MuHV-4) 的小鼠的 NK 细胞被武装，证据是颗粒酶 B 蛋白表达、细胞毒性和干扰素-γ产生增加。潜伏感染宿主中的 NK 细胞武装发生得很快，并不需要急性病毒感染。此外，由潜伏感染武装的 NK 细胞保护宿主免受致命淋巴瘤的挑战。因此，潜伏性疱疹病毒感染所创造的免疫环境提供了一种机制，使宿主 NK 细胞的功能在体内得到增强。
