Ragon Institute of Massachusetts General Hospital, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts, USA.
Mucosal Immunol. 2012 Jan;5(1):30-40. doi: 10.1038/mi.2011.40. Epub 2011 Oct 12.
The human gut mucosa is a major site of human immunodeficiency virus (HIV) infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells have an important role in control of HIV infection, but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here, we show that two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (intraepithelial lymphocytes, IELs) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective killer immunoglobulin-like receptor/human leukocyte antigen genotypes. Both IEL and LP NK cells were significantly expanded in immunological non-responsive patients, who incompletely recovered CD4+ T cells on highly active antiretroviral therapy (HAART). These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T-cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut.
人类肠道黏膜是人类免疫缺陷病毒 (HIV) 感染和感染相关发病机制的主要部位。越来越多的证据表明，自然杀伤 (NK) 细胞在控制 HIV 感染方面发挥着重要作用，但它们在肠道中介导抗病毒活性的机制尚不清楚。在这里，我们表明 NK 细胞存在于肠道中的两个不同亚群，一个定位于上皮内空间（上皮内淋巴细胞，IEL），另一个定位于固有层（LP）。在慢性感染中，这两个 NK 细胞亚群的频率都降低了，而在具有保护性杀伤免疫球蛋白样受体/人类白细胞抗原基因型的自发控制器中，IELNK 细胞保持稳定。在免疫无反应性患者中，IEL 和 LP NK 细胞均显著扩增，这些患者在高效抗逆转录病毒治疗 (HAART) 下不完全恢复 CD4+T 细胞。这些数据表明，IEL 和 LP NK 细胞可能在肠道中扩增，以弥补 CD4+T 细胞恢复受损，但只有 IELNK 细胞可能参与提供肠道中对 HIV 的持久控制。
