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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >Functional advantage of educated KIR2DL1(+) natural killer cells for anti-HIV-1 antibody-dependent activation
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Functional advantage of educated KIR2DL1(+) natural killer cells for anti-HIV-1 antibody-dependent activation

机译：受过教育的KIR2DL1（+）自然杀伤细胞对HIV-1抗体依赖性激活的功能优势

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摘要

Evidence from the RV144 HIV-1 vaccine trial implicates anti-HIV-1 antibody-dependent cellular cytotoxicity (ADCC) in vaccine-conferred protection from infection. Among effector cells that mediate ADCC are natural killer (NK) cells. The ability of NK cells to be activated in an antibody-dependent manner is reliant upon several factors. In general, NK cell-mediated antibody-dependent activation is most robust in terminally differentiated CD57(+) NK cells, as well as NK cells educated through ontological interactions between inhibitory killer immunoglobulin-like receptors (KIR) and their major histocompatibility complex class I [MHC-I or human leucocyte antigen (HLA-I)] ligands. With regard to anti-HIV-1 antibody-dependent NK cell activation, previous research has demonstrated that the epidemiologically relevant KIR3DL1/HLA-Bw4 receptor/ligand combination confers enhanced activation potential. In the present study we assessed the ability of the KIR2DL1/HLA-C2 receptor/ligand combination to confer enhanced activation upon direct stimulation with HLA-I-devoid target cells or antibody-dependent stimulation with HIV-1 gp140-pulsed CEM.NKr-CCR5 target cells in the presence of an anti-HIV-1 antibody source. Among donors carrying the HLA-C2 ligand for KIR2DL1, higher interferon (IFN)- production was observed within KIR2DL1(+) NK cells than in KIR2DL1(-) NK cells upon both direct and antibody-dependent stimulation. No differences in KIR2DL1(+) and KIR2DL1(-) NK cell activation were observed in HLA-C1 homozygous donors. Additionally, higher activation in KIR2DL1(+) than KIR2DL1(-) NK cells from HLA-C2 carrying donors was observed within less differentiated CD57(-) NK cells, demonstrating that the observed differences were due to education and not an overabundance of KIR2DL1(+) NK cells within differentiated CD57(+) NK cells. These observations are relevant for understanding the regulation of anti-HIV-1 antibody-dependent NK cell responses.
机译：RV144 HIV-1疫苗试验的证据表明抗HIV-1抗体依赖性细胞毒性（ADCC）可预防疫苗感染。在介导ADCC的效应细胞中有自然杀伤（NK）细胞。 NK细胞以抗体依赖性方式被激活的能力取决于几个因素。通常，NK细胞介导的抗体依赖性激活在最终分化的CD57（+）NK细胞以及通过抑制性杀伤性免疫球蛋白样受体（KIR）与主要组织相容性复合体I类之间的本体相互作用所教育的NK细胞中最为强劲[MHC-1或人白细胞抗原（HLA-1）]配体。关于抗HIV-1抗体依赖性NK细胞活化，先前的研究表明，与流行病学相关的KIR3DL1 / HLA-Bw4受体/配体组合具有增强的活化潜能。在本研究中，我们评估了KIR2DL1 / HLA-C2受体/配体组合在直接用缺乏HLA-1的靶细胞直接刺激或用HIV-1 gp140脉冲的CEM.NKr-进行抗体依赖性刺激时赋予增强的激活的能力。在抗HIV-1抗体源的存在下，CCR5靶向细胞。在带有针对KIR2DL1的HLA-C2配体的供体中，在直接和抗体依赖性刺激下，在KIR2DL1（+）NK细胞中观察到的干扰素（IFN）产生高于在KIR2DL1（-）NK细胞中。在HLA-C1纯合供体中未观察到KIR2DL1（+）和KIR2DL1（-）NK细胞激活的差异。此外，在分化程度较低的CD57（-）NK细胞中观察到KIR2DL1（+）的活化高于HLA-C2携带供体的KIR2DL1（-）NK细胞，这表明观察到的差异是由于教育而不是KIR2DL1（过量）引起的。 +）分化的CD57（+）NK细胞内的NK细胞。这些观察结果与理解抗HIV-1抗体依赖性NK细胞应答的调节有关。

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