Altered distribution of mucosal NK cells during HIV infection
Altered distribution of mucosal NK cells during HIV infection
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DOI：
10.1038/mi.2011.40
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发表时间：
2012-01-01
影响因子：
8
通讯作者：
Alter, G.
中科院分区：
文献类型：
--
作者：
Sips, M.;Sciaranghella, G.;Alter, G.
人类肠道粘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感染中起着重要作用，但它们介导肠道抗病毒活性的机制尚不清楚。在这里，我们发现，两个不同的NK细胞亚群存在于肠道，一个定位于上皮内空间（上皮内淋巴细胞，IELS）和其他固有层（LP）。NK细胞的两个子集的频率在慢性感染中降低，而IEL NK细胞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者中保持稳定。IEL和LP NK细胞在免疫无应答患者中显著扩增，这些患者在高效抗逆转录病毒治疗（HAART）中未完全恢复CD 4 + T细胞。这些数据表明，IEL和LP NK细胞都可能在肠道中扩增，以弥补受损的CD 4 + T细胞恢复，但只有IEL NK细胞可能参与对肠道中HIV的持久控制。
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.