Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes
Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes
复制标题
DOI：
10.4049/jimmunol.171.10.5396
复制
发表时间：
2003-11-15
影响因子：
4.4
通讯作者：
Riley, EM
中科院分区：
文献类型：
--
作者：
Artavanis-Tsakonas, K;Eleme, K;Riley, EM
当来自非免疫供体的PBMC暴露于体外恶性疟原虫感染的红细胞（iRBC）时，人类NK细胞是保护性细胞因子ifn - γ的最早来源。在这项研究中，我们发现人类NK细胞与iRBC形成稳定的偶联物，但不与未感染的RBC形成偶联物，并且诱导ifn - γ合成依赖于NK细胞与iRBC之间的直接接触。NK细胞仅在IL-12/IL-18来源存在时才对iRBC产生反应，并且优先对iRBC产生反应的NK细胞亚群表达高水平的凝集素样受体CD94/NKG2A。献血者对iRBC的反应能力存在异质性。DNA分析揭示了供体人群中杀手igg样受体（KIR）基因型的相当大的异质性，并在非洲和亚洲血统的供体中发现了21个新的KIR等位基因变异。重要的是，我们发现了KIR基因型和NK对iRBC反应性之间存在显著关联的证据。这强调需要大规模的基于人群的研究来解决KIR基因型和疟疾易感性之间的关系。
Human NK cells are the earliest source of the protective cytokine IFN-gamma when PBMC from nonimmune donors are exposed to Plasmodium falciparum-infected RBC (iRBC) in vitro. In this study, we show that human NK cells form stable conjugates with iRBC but not with uninfected RBC and that induction of IFN-gamma synthesis is dependent on direct contact between the NK cell and the iRBC. NK cells respond to iRBC only in the presence of a source of IL-12/IL-18 and the subset of NK cells that preferentially respond to iRBC express high levels of the lectin-like receptor CD94/NKG2A. There is heterogeneity between donors in their ability to respond to iRBC. DNA analysis has revealed considerable heterogeneity of killer Ig-like receptor (KIR) genotype among the donor population and has identified 21 new KIR allelic variants in the donors of African and Asian descent. Importantly, we find evidence for significant associations between KIR genotype and NK responsiveness to iRBC. This emphasizes the need for large-scale population-based studies to address associations between KIR genotype and susceptibility to malaria.