Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals
Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals
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DOI：
10.3390/v11030239
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发表时间：
2019-03-09
期刊：
影响因子：
4.7
通讯作者：
Grant, Michael D.
中科院分区：
文献类型：
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作者：
Comeau, Emilie M.;Holder, Kayla A.;Grant, Michael D.
表达NKG2C的自然杀伤（NK）细胞的扩增发生在人巨细胞病毒（HCMV）感染后，并通过人免疫缺陷病毒（HIV）共感染扩增。这些表达NKG2C的NK细胞表现出增强的CD16依赖性细胞因子产生，并下调Fc γ RI γ和早幼粒细胞白血病锌指蛋白（PLZF）。缺乏NKG2C会降低对HIV感染的抵抗力，但这是否会影响NK细胞获得上级抗体依赖性功能尚不清楚。因此，我们的目的是研究NKG2C（空）HIV感染者中HCMV驱动的NK细胞分化是否受损。在HIV感染的NKG2C（无效）和NKG2C表达组之间比较了表型（CD2、CD16、CD57、NKG2A、Fc β RI γ和PLZF表达）和功能（细胞因子诱导和细胞毒性）特性。通过天然细胞毒性受体或通过CD16刺激后比较细胞因子的产生。通过抗CD16重定向裂解和针对抗I类人白细胞抗原（HLA）抗体包被细胞的经典抗体依赖性细胞介导的细胞毒性（ADCC）测定细胞毒性。我们的数据表明，在有或没有NKG2C的HIV感染中，HCMV驱动的NK细胞分化高度相似。虽然表达CD2（p = 0.009）或共表达CD2和CD16（p = 0.03）的成熟（CD57（pos））NK细胞的分数在NKG2C（null）HIV感染个体中显著较高，但NKG2A、Fc ε RI γ或PLZF表达无显著差异。观察到的一般表型和功能等效性表明HCMV驱动的NK细胞分化的NKG2C非依赖性途径，可能涉及CD2表达增加。
Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate Fc epsilon RI gamma and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2C(null) HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, Fc epsilon RI gamma, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV-infected NKG2C(null) and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57(pos)) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2C(null) HIV-infected individuals, there were no significant differences in NKG2A, Fc epsilon RI gamma, or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression.