Natural Killer Cells Adapt to Cytomegalovirus Along a Functionally Static Phenotypic Spectrum in Human Immunodeficiency Virus Infection.
Natural Killer Cells Adapt to Cytomegalovirus Along a Functionally Static Phenotypic Spectrum in Human Immunodeficiency Virus Infection.
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DOI：
10.3389/fimmu.2018.02494
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发表时间：
2018
影响因子：
7.3
通讯作者：
Grant MD
中科院分区：
文献类型：
--
作者：
Holder KA;Lajoie J;Grant MD
与HCMV感染相关的事件驱动功能增强的CD 57 posNKG 2Cpos适应性NK细胞的积累。我们研究了NK细胞适应HCMV沿着一个拟议的连续不断的进展，从急性激活，通过成熟和记忆形成的功能衰竭。急性暴露于HCMV感染后24小时收集的条件培养基（HCMVsn）增加了所有HCMV血清阴性和血清阳性供者的NK细胞毒性，自然和抗体依赖性细胞介导的细胞毒性（ADCC）分别平均增加38%和29%。通过阻断I型干扰素（IFN）受体完全消除了NK细胞细胞毒性的增加，并且在HCMVsn中存在的相同浓度下单独暴露于IFN-α2时发生了等效应答。为了研究HCMV感染的长期影响，我们集中于三组人类免疫缺陷病毒（HIV）感染的受试者，其区分为HCMV血清阴性或HCMV血清阳性，其NK细胞表达NKG 2C的分数高（>20%）或低（<6%）。所有三个HIV感染组的NK细胞对HCMVsn和IFN-α2的应答方式与HCMV血清阴性或血清阳性对照组的NK细胞相似。与HIV感染组相比，HCMV状态和HCMV感染适应表型证据的程度均未显著影响ADCC或CD 16介导的NK细胞脱粒和IFN-γ产生的平均水平。IFN-γ产生水平与缺乏FcεRIγ（FcRγ）的NK细胞比例显著相关，但与表达NKG 2C的NK细胞比例无关。在任何组中，NK细胞上的耗竭标志物Lag-3和PD-1的表达可忽略不计，并且在表达Tim-3的NK细胞的分数方面，组间无显著差异。表达Tim-3的NK细胞的分数不受CD 16刺激的影响。相对于总的NK细胞群体，Tim-3表达细胞对CD 16刺激的反应在HCMV血清阴性和血清阳性组中受到严重损害。一般而言，HIV感染中NK细胞对CD 16信号传导的应答功能得到了很好的保留，尽管HCMV对NK细胞FcRγ和NKG 2C表达有明显影响，但几乎没有证据表明HIV感染中对HCMV感染的适应水平影响了CD 16依赖性NK细胞信号传导。
Events related to HCMV infection drive accumulation of functionally enhanced CD57posNKG2Cpos adapted NK cells. We investigated NK cell adaptation to HCMV along a proposed continuum progressing from acute activation through maturation and memory formation towards functional exhaustion. Acute exposure to conditioned medium collected 24 h after HCMV infection (HCMVsn) increased NK cell cytotoxicity for all HCMV-seronegative and seropositive donors tested, with mean 38 and 29% boosts in natural and antibody-dependent cell-mediated cytotoxicity (ADCC), respectively. Increases in NK cell cytotoxicity were completely abrogated by blocking type I interferon (IFN) receptors and equivalent responses occurred with exposure to IFN-α2 alone at the same concentration present in HCMVsn. To study longer term effects of HCMV infection, we focused on three groups of human immunodeficiency virus (HIV)-infected subjects distinguished as HCMV-seronegative or HCMV-seropositive with either high (>20%) or low (<6%) fractions of their NK cells expressing NKG2C. The NK cells of all three HIV-infected groups responded to HCMVsn and IFN-α2 in a manner similar to the NK cells of either HCMV-seronegative or seropositive controls. Neither HCMV status, nor the extent of phenotypic evidence of adaptation to HCMV infection significantly affected mean levels of ADCC or CD16-mediated NK cell degranulation and IFN-γ production compared between the HIV-infected groups. Levels of IFN-γ production correlated significantly with the fraction of NK cells lacking FcεRIγ (FcRγ), but not with the fraction of NK cells expressing NKG2C. There was negligible expression of exhaustion markers Lag-3 and PD-1 on NK cells in any of the groups and no significant difference between groups in the fraction of NK cells expressing Tim-3. The fraction of NK cells expressing Tim-3 was unaffected by CD16 stimulation. Relative to the total NK cell population, responses of Tim-3-expressing cells to CD16 stimulation were variably compromised in HCMV seronegative and seropositive groups. In general, NK cell function in response to signaling through CD16 was well preserved in HIV infection and although HCMV had a clear effect on NK cell FcRγ and NKG2C expression, there was little evidence that the level of adaptation to HCMV infection affected CD16-dependent NK cell signaling in HIV infection.
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影响因子：
7.3
作者：
Kared H;Martelli S;Tan SW;Simoni Y;Chong ML;Yap SH;Newell EW;Pender SLF;Kamarulzaman A;Rajasuriar R;Larbi A
通讯作者：
Larbi A
影响因子：
8.8
作者：
Hadaya, K.;de Rham, C.;Villard, J.
通讯作者：
Villard, J.
影响因子：
56.9
作者：
Brown, MG;Dokun, AO;Yokoyama, WM
通讯作者：
Yokoyama, WM
影响因子：
20.3
作者：
Gumá, M;Angulo, A;López-Botet, M
通讯作者：
López-Botet, M
人类巨细胞病毒驱动NKG2CHI天然杀伤细胞中IFNG基因座的表观遗传印记。
影响因子：
6.7
作者：
Luetke-Eversloh M;Hammer Q;Durek P;Nordström K;Gasparoni G;Pink M;Hamann A;Walter J;Chang HD;Dong J;Romagnani C
通讯作者：
Romagnani C