Frequent and strong antibody-mediated natural killer cell activation in response to HIV-1 Env in individuals with chronic HIV-1 infection.
Frequent and strong antibody-mediated natural killer cell activation in response to HIV-1 Env in individuals with chronic HIV-1 infection.
复制标题
在慢性 HIV-1 感染个体中，针对 HIV-1 Env 的频繁而强烈的抗体介导的自然杀伤细胞激活。
DOI：
10.1128/jvi.00569-12
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发表时间：
2012
影响因子：
5.4
通讯作者：
Altfeld,Marcus
中科院分区：
文献类型：
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作者：
Thobakgale,ChristinaF;Fadda,Lena;Lane,Kimberly;Toth,Ildiko;Pereyra,Florencia;Bazner,Suzane;Ndung'u,Thumbi;Walker,BruceD;Rosenberg,EricS;Alter,Galit;Carrington,Mary;Allen,ToddM;Altfeld,Marcus
自然杀伤细胞(NK细胞)在控制HIV-1感染中起着关键作用，最近对NK细胞对HIV-1多肽的反应进行了描述。然而，NK细胞识别HIV-1抗原的机制尚不完全清楚。我们用全血分析和多参数流式细胞术研究了早期和慢性HIV-1 B分支感染过程中HIV-1多肽对NK细胞活化的影响。在未感染HIV-1的个体中，未检测到抗体介导的NK细胞对HIV-1多肽的激活。相比之下，79%的慢性感染者和22%的早期感染者对HIV-1抗原有可检测到的干扰素(γ)NK细胞反应(P<；0.00001)。产生干扰素-γ和肿瘤坏死因子-α的NK细胞最常针对Env gp120(中位数为4%，范围为所有NK细胞的0%至31%)。NK细胞很少针对其他HIV-1蛋白，如Gag、Pol和Nef。抗体介导的NK细胞对多肽的反应主要与Env蛋白结合，需要血浆或血浆免疫球蛋白G的存在，并导致NK细胞表面CD16表达降低，提示NK细胞是由抗体介导的激活。需要进一步的研究来评估这些抗体介导的NK细胞反应对HIV-1疾病进展和疫苗诱导的感染保护的后果。
Natural killer (NK) cells play a critical role in the control of HIV-1 infection, and NK cells that respond to HIV-1 peptides have been recently described. However, the mechanisms by which NK cells recognize HIV-1 antigens are not fully understood. We investigated NK cell activation in response to HIV-1 peptides during early and chronic HIV-1 clade B infection using a whole-blood assay and multiparameter flow cytometry. Antibody-mediated NK cell activation in response to HIV-1 peptides was not detected in HIV-1-uninfected individuals. In contrast, 79% of individuals with chronic infection and 22% of individuals with early infection had detectable gamma interferon (IFN-γ) NK cell responses to HIV-1 antigens (P< 0.00001). IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing NK cells most frequently targeted Env gp120 (median of 4% and range of 0 to 31% of all NK cells). NK cells rarely targeted other HIV-1 proteins such as Gag, Pol, and Nef. Antibody-mediated NK cell responses to peptides mapped predominantly to Env protein, required the presence of plasma or plasma IgG, and resulted in lower CD16 expression on NK cells, suggesting an antibody-mediated activation of NK cells. Further studies are needed to assess the consequences of these antibody-mediated NK cell responses for HIV-1 disease progression and vaccine-induced protection from infection.