新生儿细菌性肺炎患者外周血自然杀伤细胞的数量变化及其临床意义

目的检测新生儿细菌性肺炎患者外周血总自然杀伤细胞(NK细胞)及其各亚群百分率的变化,探讨NK细胞在其发病中的临床意义。方法采用流式细胞术检测38例新生儿细菌性肺炎患者及18例正常新生儿的总NK细胞及其各亚群占外周血总淋巴细胞百分率,住院天数在10 d以内(含10 d)为A组、住院天数10 d以上为B组;入院时外周血白细胞的数量5.0×109/L或20.0×109/L者为重度感染组,5.0×109/L外周血白细胞数量20.0×109/L者为轻度感染组。结果新生儿细菌性肺炎患者外周血总NK细胞及CD3-CD56negCD16bright百分率低于正常新生儿(P0.01),但NK细胞CD3-CD56bright CD16neg/dim及CD3-CD56dimCD16bright亚群差异无统计学意义。A组CD3-CD56negCD16bright亚群百分率低于正常新生儿(P0.01),而总NK细胞及其他亚群则差异无统计学意义。B组总NK细胞及CD3-CD56negCD16bright亚群百分率低于正常新生儿(P0.01),且B组总NK细胞及各亚群百分率低于A组(P0.05)。重度感染组总NK细胞及其各亚群百分率明显低于轻度感染组,差异有统计学意义(P0.05)。结论新生儿细菌性肺炎患者病情越重住院时间越长,总NK细胞及其各亚群百分率越低。     

HIV感染后CD8~+T细胞表面NK相关受体表达的变化

目的深入了解人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染后CD8+T细胞表面NK相关受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV感染者、11例AIDS患者、15例进行高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)者和13例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血CD8+T细胞表面NKG2D、NKG2A和KIR3DL1的表达。结果 HIV感染后CD8+T细胞表面NKG2D表达的百分比显著低于健康对照,NKG2D+NKG2A-表达的百分比随疾病进展逐渐下降,且NKG2D+NKG2A-表达的百分比与CD4+T细胞的绝对数量呈正相关。AIDS患者CD8+T细胞表达NKG2A显著高于其它各组,随着疾病的进展CD8+T细胞表达NKG2A+NKG2D-百分比逐渐上升,AIDS患者显著高于其它各组,经抗逆转录病毒治疗后下降至健康对照的水平,且NKG2A+NKG2D-表达的百分比与CD4+T细胞的绝对数量呈负相关。HIV感染后CD8+T细胞KIR3DL1+表达的百分比较健康对照并无显著差异。结论 HIV感染机体后,CD8+T细胞NK相关受体表达变化与疾病进展相关,抗病毒治疗后可恢复其变化。     

HIV感染后CD4~+ T细胞表面NK相关受体表达的变化

目的研究人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染后CD4+T细胞表面NK相关受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV感染者、11例AIDS患者、15例进行高效抗逆转录病毒治疗(highly activeantiretroviral therapy,HAART)者和13例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血CD4+T细胞表面NKG2D、NKG2A和KIR3DL1的表达。结果 AIDS患者CD4+T细胞表面NKG2D表达的百分比显著高于其他各组,且NKG2D表达的百分比与CD4+T细胞的绝对数量呈负相关(R=-0.352,P<0.05),与HIV病毒载量呈正相关(R=0.426,P<0.05)。AIDS患者CD4+T表面NKG2A表达的百分比显著高于其他各组,NKG2A+NKG2D-表达的百分比显著高于其他各组,且NKG2A表达的百分比与CD4+T细胞的绝对数量呈负相关(R=-0.432,P<0.01)。结论 HIV感染机体后,CD4+T细胞NK相关受体表达变化与疾病进展相关。     

结核性胸液中NK细胞的亚群及表型功能特征分析

目的探讨结核性胸液(PFC)中NK细胞的亚群分布及表型功能特征。方法以正常人外周血单个核细胞(PBMC)作对照,利用多种标记抗体进行表面和细胞内细胞毒效应分子染色,再利用流式细胞仪在单个细胞水平上分析结核性胸水中NK细胞亚群的异质性和生物学特征。结果 NK细胞可以分为CD56+CD16-、CD56+CD16+和CD56-CD16+三个亚群,与PBMC中的NK细胞相比,PFC中CD56+CD16-NK细胞亚群明显增加,而CD56+CD16+NK细胞亚群比例明显下降;结核性胸液中CD56+CD16-及CD56+CD16+NK细胞亚群表达较低水平的颗粒酶B,CD107a/b的比例在结核性胸液中3个NK细胞亚群中均有增加(P<0.05)。结核性胸液中NK细胞表达高水平表面抑制性受体NKG2A及表面活化性受体NKG2D。活化分子CD69及CD25在结核性胸水中NK细胞上的表达均有所增加(P<0.05)。结论结核性胸液中的NK细胞比例与PBMC相比发生变化,结核性胸液中的NK细胞表达低水平杀伤分子颗粒酶B但表达高水平活化分子CD69,提示NK细胞在结核感染中发挥其生物学功能。     

HIV感染者外周血CD8~+NK细胞百分比及功能变化研究

目的探讨HIV感染者外周血中CD8~+NK细胞百分比的变化与表达CD107a的能力。方法选取未经高效抗逆转录病毒疗法(highly active antiretroviral therapy,HAART)治疗的HIV慢性感染者,感染者按照CD4~+T细胞数量分成高、低2组,用流式细胞仪检测其外周CD8~+NK细胞百分比的变化情况和CD107a的表达量。结果 HIV感染者外周血中CD8~+NK细胞的百分比明显低于正常人(P=0.011 1),CD8~+NK细胞的百分比与病毒载量成明显的负相关关系(r=-0.541 9,P=0.045 3)。K562细胞系刺激后,CD4~+T细胞高组CD107a的表达量明显增高。结论具有抗病毒作用的CD8~+NK细胞在HIV感染后百分比下降;CD8~+NK细胞水平高以及功能较强者HIV病毒水平相对降低,CD4~+T细胞数量相对高。     

中国HIV感染者细胞毒性淋巴细胞内穿孔素的差异性表达

目的 了解中国HIV感染者细胞毒性相关的NK细胞及CD8^＋T细胞内穿孔素表达水平，探讨HIV感染过程中穿孔素表达与机体免疫功能的关系。方法 采集31例未经抗病毒治疗的HIV感染者和经过高效抗逆转录病毒疗法（HAAS）治疗的17例HIV／AIDS患者以及15例健康对照的抗凝全血，应用流式细胞仪胞内染色法检测CD56^＋／CD3^-、CD3^-／CD16^＋NK细胞及CD8^＋／CD3^＋内穿孔素表达的百分数，分析其与NK细胞绝对值、NK细胞百分数、CD4^＋T、CD8^＋T淋巴细胞绝对值及血浆病毒载量的相关性。结果 中国HIV感染者的NK细胞CD56^＋／CD3^-及CD3^-／CD16^＋亚群穿孔素表达百分数（平均13．17％，平均24．05％）高于CD8^＋T细胞穿孔素表达百分数（平均9．03％）；NK细胞内穿孔素表达低于健康对照（P〈0．05，P〈0．05），CD8^＋T细胞内穿孔素表达高于健康对照（P〈0．05）；NK细胞及CD8^＋T细胞内穿孔素表达水平与其绝对计数显著相关，与疾病进展不相关。HAART治疗组NK细胞内穿孔素表达升高，CD8T^＋细胞内穿孔素表达无显著变化。结论 中国HIV感染者NK细胞内穿孔素表达降低，抗病毒治疗后升高；CD8^＋T细胞内穿孔素表达升高，抗病毒治疗后无显著变化。     

丙型肝炎患者外周血淋巴细胞亚群变化特点

目的观察丙型肝炎患者外周血淋巴细胞亚群变化特点。方法对219例丙型肝炎患者和66例健康对照者分别采用流式细胞术(FCM)检测外周血CD45+淋巴细胞,T淋巴细胞(CD45+CD3+、CD45+CD3+CD4+、CD45+CD3+CD8+),B淋巴细胞(CD45+CD3-CD19+),NK细胞(CD45+CD3-CD16+56+)百分比和细胞绝对计数。结果在丙型肝炎病毒(HCV)慢性感染到肝硬化失代偿过程中,淋巴细胞亚群绝对计数出现逐渐下降趋势。慢性丙型肝炎组较健康对照组CD4+T细胞、CD8+T细胞、NK细胞绝对计数明显降低(P0.05)。丙型肝炎肝硬化在早期组和失代偿期组淋巴细胞各亚群计数均较慢性丙型肝炎组明显降低(P0.01),而失代偿期组明显低于早期组(P0.01)。B淋巴细胞百分比以及CD4/CD8比值在慢性感染到肝硬化失代偿过程中出现升高趋势,并在丙型肝炎肝硬化早期和失代偿期时变化明显(P0.01,P0.05),NK淋巴细胞百分比出现明显降低趋势(P0.01)。结论 HCV感染慢性化至肝硬化早期和失代偿期的过程中,外周血CD8+T细胞、CD4+T细胞、NK细胞减少;B细胞百分比、CD4/CD8比值升高。     

HAART对人类免疫缺陷病毒感染者淋巴细胞亚群的影响

应用流式细胞分析法通过分析检测41例AIDS患者与30例健康对照之间,以及21例AIDS患者在接受HAART治疗前后外周血淋巴细胞亚群的表达情况,研究感染HIV病毒以及HAART治疗对淋巴细胞亚群的影响。结果显示AIDS患者与健康对照相比,外周血CD4~+CD45RA~+、CD4~+CD28~+、CD4~+CD45RO~+、CD4~+CD95~+细胞比例明显低于正常对照,CD8~+CD95~+、CD8~+CD38~+、CD56~+细胞比例明显高于正常对照;经HAART治疗后,CD4~+CD45RA~+,CD4~+CD28~+细胞比例比治疗前升高,CD56~+细胞比例比治疗前显著下降。结果表明CD4~+T淋巴细胞表面CD45RA、CD28表达,以及CD56~+细胞能够预测AIDS患者HAART治疗效果。     

HIV-1感染对NK细胞及其活化性受体CD226表达的影响

目的　评价HIV 1感染对NK细胞以及CD2 2 6 /PTA1表达的影响。方法　采用流式细胞术分析了 2 7例HIV 1感染者以及 16例健康献血员NK细胞相关膜抗原 ,用HIV 1SF3 3 株体外感染外周血单个核细胞 (PBMC) ,进行NK细胞活化表达CD2 2 6的动态观察。结果　 2 7例HIV 1感染者均处于无症状感染期 ,CD16 + CD3-、CD8+ CD3-细胞亚群百分率和绝对数均低于健康对照 (P <0 .0 5 ) ,CD16 + CD3-和CD8+ CD3-细胞中表达CD2 2 6的细胞比例显著高于对照 (P <0 .0 5 )。HIV 1和PHA均可体外诱导CD2 2 6在CD16 + NK细胞表面高水平表达。结论　CD2 2 6分子可能参与HIV 1感染诱导的NK细胞活化机制。     

不明原因自然流产与蜕膜NK细胞表面活化性受体表达的相关性研究

探讨不明原因自然流产患者蜕膜NK细胞杀伤活性与其细胞表面活化性受体NKp46、NKp44、NKp30和NKG2D表达的相关性。选取21例早孕不明原因自然流产患者为病例组,25例正常早孕人流妇女为对照组,收集两组的蜕膜组织,Ficoll密度梯度离心分离淋巴细胞,MACS磁珠分选CD3-CD56+NK细胞。以K562细胞为靶细胞,用细胞染色及流式细胞技术检测两组蜕膜NK细胞杀伤活性,用流式细胞技术检测两组蜕膜CD56brightCD16-NK和CD56dimCD16+NK细胞上活化性受体NKp46、NKp44、NKp30和NKG2D的表达,并与NK细胞杀伤活性进行相关性分析。结果:(1)早孕蜕膜NK细胞具有杀伤活性;(2)病例组蜕膜NK细胞的杀伤活性较正常对照组显著增强(P=0.014);(3)病例组蜕膜CD56brightCD16-NK细胞中NKp44的表达比正常对照组显著升高(P=0.021);病例组蜕膜CD56dimCD16+NK细胞中NKp46和NKp44的表达比正常对照组显著升高(分别P=0.026,P=0.041);其余活化性受体的表达两组未见明显差异;(4)蜕膜NK细胞杀伤功能与蜕膜CD56brightCD16-NK细胞中NKp44的表达呈显著正相关(r=0.677,P<0.05),和蜕膜CD56dimCD16+NK细胞中NKp46的表达呈显著正相关(r=0.634,P<0.05)。蜕膜NK细胞活化性受体NKp46和NKp44表达增加,从而使蜕膜NK细胞的杀伤功能增强可能在不明原因自然流产的发病中起重要作用。     

人外周血NK细胞亚群、表型和生物学特征

目的：探讨人外周血NK细胞的异质性和生物学特征。方法：利用多种标记抗体进行细胞表面和细胞内细胞毒效应分子染色，再利用流式细胞仪在单个细胞水平上分析NK细胞亚群的多样性和生物学特征。结果：NK细胞可分为CD56^ 、CD56^ ’CD16^ 和CD16^ 三个亚群。所有CD56^ NK细胞均表达CD95，但表达水平的高(CD95^bright)和低(CD95^dim)不同。在CD95^bright和CD8^ 细胞亚群中有43．5％的细胞同时表达颗粒酶B和穿孔素。而CD56^ CD16^ 和CD16^ 细胞表达CD95均为CD95^bright，同时表达颗粒酶B(83．6％)和穿孔素(89．8％)。结论：NK细胞乃异质性群体，随着CD56表达减少和CD16表达增加。其生物效应功能逐渐成熟。     

Impaired IFN-γ production and proliferation of NK cells in multiple sclerosis

NK cells are multicompetent lymphocytes of the innate immune system with a central role in host defense and immune regulation. Studies in experimental animal models of multiple sclerosis (MS) provided evidence for both pathologic and protective effects of NK cells. Humans harbor two functionally distinct NK-cell subsets exerting either predominantly cytotoxic (CD56(dim)CD16(+)) or immunoregulatory (CD56(bright)CD16(-)) functions. We analyzed these two subsets and their functions in the peripheral blood of untreated patients with relapsing-remitting MS compared with healthy blood donors. While ex vivo frequencies of CD56(bright)CD16(-) and CD56(dim)CD16(+) NK cells were similar in patients and controls, we found that cytokine-driven in vitro accumulation and IFN-γ production of CD56(bright)CD16(-) NK cells but not of their CD56(dim)CD16(+) counterparts were substantially diminished in MS. Impaired expansion of CD56(bright)CD16(-) NK cells was cell intrinsic because the observed effects could be reproduced with purified NK cells in an independent cohort of patients and controls. In contrast, cytolytic NK-cell activity toward the human erythromyeloblastoid leukemia cell line K562, the allogeneic CD4(+) T cell line CEM and allogeneic primary CD4(+) T-cell blasts was unchanged. Thus, characteristic functions of CD56(bright)CD16(-) NK cells, namely cytokine-induced NK cell expansion and IFN-γ production, are compromised in the NK cell compartment of MS patients.     

Lymphocyte and NK cell subpopulations in HIV seronegative Thais

Lymphocyte subpopulations, i.e. T, B and natural killer (NK) cells including NK cell subsets which express CD16 molecules (with or without co-expression of CD56 molecules) and NK cell subsets which express CD56 molecules (with or without co-expression of CD16 molecules) were enumerated by two color-flow cytometry in a total of 125 HIV seronegative Thai adults. The study demonstrated relatively low CD4 counts in the subjects, i.e. 26.3% of them had a CD4 count of less than 500 cells/microl. In contrast, their NK cell counts were relatively high. Statistical analyses of the percentage values showed that females had significantly higher CD3 (total T cells), but lower NK cell counts as compared to males (p < 0.05). Regarding age variation, an increase of 1.1% of CD4 cells per decade was seen. It was roughly estimated that about 86% of NK cells harbored both CD16 and CD56 molecules. Collective data from several studies including the present one suggest that high NK cell counts may be a compensation for low CD4 cell counts in Mongoloid people. Thus, the role of NK cells in the defense cascade against viral infections, especially human immunodeficiency virus infections deserves further investigation.     

Proliferative and cytotoxic capabilities of CD16+CD56- and CD16+/-CD56+ natural killer cells

Natural killer (NK) cells can be divided into several subpopulations according to their expression of the surface antigens CD16 and CD56. The modest quantity of NK cells in the blood available for functional analysis has been a limitation in studies of NK cell subpopulations. In the present study, epinephrine infusion was used to induce lymphocytosis before immunomagnetic methods were applied to isolate CD16+/-CD56+ and CD16+CD56- CD3- NK cells. These subpopulations were compared according to their proliferative and cytotoxic capabilities in 10 human immunodeficiency virus (HIV)-infected individuals and 5 healthy controls. The CD16+CD56- NK cell subgroup had a higher proliferative capacity, whereas the CD16+/-CD56+ NK cell subgroup was mainly cytotoxic, and unaffected by HIV serostatus. This study thus suggests that NK cell phenotypes more strongly predict NK cell function than HIV serostatus. This assertion should be considered when studying NK cell function in subjects with a deviating composition of NK cells.     

Phenotypic and functional heterogeneity of natural killer cells from umbilical cord blood mononuclear cells

Natural killer cells (NK) from umbilical cord blood (CB) play an important role in allogeneic stem cell transplantation and defending infections of newborn. Based on the surface expression of CD56 and CD16 or inhibitory and activatory receptors, NK cells could be subdivided into various subsets with distinct functions. To investigate the biological characterization of NK subsets, the phenotypes and intracellular proteins in freshly isolated CB NK subsets were analyzed at the single cell level by flow cytometry in current study. The production of IFN-gamma and cytotoxicity against K562 target cells were also evaluated after stimulation with IL-12. The results showed that NK cells from CB could be divided into four subsets on the basis of CD56 and CD16 expression. Interestingly, CB NK cells expressed CD45RA but not CD45RO molecules that is similar to the na?ve T cells. Moreover, CD27, a memory T cell marker, highly expressed on CD56(hi)CD16- NK cells. The killing-associated molecules, NKG2A, NKG2D, CD95 and the intracellular granzyme B and perforin were heterogeneously expressed among the 4 subsets. Addition of IL-12 into cultures resulted in the induction of IFN-gamma expression by CD56(hi)CD16- and CD56(lo)CD16- subsets and the enhancement of NK cytolytic activity. Taken together, this study elucidated the heterogeneity in phenotypes and biological functions of CB NK cells.     

Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infection

Human natural killer (NK) (CD3- CD56+) cells can be divided into two functionally distinct subsets, CD3- CD56(dim) and CD3- CD56(bright). We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3- CD56(dim) subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27- and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27(high) and CD70(high) NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus.     

Differences in activation and tissue homing markers of natural killer cell subsets during acute dengue infection

Dengue virus (DENV) infection is considered one of the most important mosquito‐borne diseases. It causes a spectrum of illness that could be due to qualitative and/or quantitative difference(s) of the natural killer (NK) cell responses during acute DENV infection. This view prompted us to perform a detailed phenotypic comparative characterization of NK cell subsets from DENV‐infected patients with dengue fever (DF), patients with dengue haemorrhagic fever (DHF) and healthy controls. The activation/differentiation molecules, CD69 and CD57 and a variety of tissue homing molecules were analysed on the CD56^hi CD16^? and CD56^lo CD16⁺ NK cells. Although there was no increase in the frequency of the total NK cells during DENV infection compared with the healthy individuals, there was a significant increase in the frequency of the CD56^hi CD16^? subset and the frequency of CD69 expression by both NK cell subsets during the febrile phase of infection. We also found an increase in the frequencies of cells expressing CD69 and CD57 in the CD56^lo CD16⁺ subset compared with those in the CD56^hi CD16^? subset. Moreover, although the CD56^lo CD16⁺ subset contained a high frequency of cells expressing skin‐homing markers, the CD56^hi CD16^? subset contained a high frequency of cells expressing bone marrow and lymph node trafficking markers. Interestingly, no differences of these NK cell subsets were noted in samples from patients with DF versus those with DHF. These findings suggest that activation and differentiation and the patterns of tissue homing molecules of the two major NK cell subsets are different and that these might play a critical role in the immune response against acute DENV infection.     

Phenotypic and Functional Heterogeneity of Natural Killer Cells from Umbilical Cord Blood Mononuclear Cells

Natural killer cells (NK) from umbilical cord blood (CB) play an important role in allogeneic stem cell transplantation and defending infections of newborn. Based on the surface expression of CD56 and CD16 or inhibitory and activatory receptors, NK cells could be subdivided into various subsets with distinct functions. To investigate the biological characterization of NK subsets, the phenotypes and intracellular proteins in freshly isolated CB NK subsets were analyzed at the single cell level by flow cytometry in current study. The production of IFN-γ and cytotoxicity against K562 target cells were also evaluated after stimulation with IL-12. The results showed that NK cells from CB could be divided into four subsets on the basis of CD56 and CD16 expression. Interestingly, CB NK cells expressed CD45RA but not CD45RO molecules that is similar to the naïve T cells. Moreover, CD27, a memory T cell marker, highly expressed on CD56^hiCD16^? NK cells. The killing-associated molecules, NKG2A, NKG2D, CD95 and the intracellular granzyme B and perforin were heterogeneously expressed among the 4 subsets. Addition of IL-12 into cultures resulted in the induction of IFN-γ expression by CD56^hiCD16^? and CD56^loCD16^? subsets and the enhancement of NK cytolytic activity. Taken together, this study elucidated the heterogeneity in phenotypes and biological functions of CB NK cells.     

Selective depletion of CD56(dim) NK cell subsets and maintenance of CD56(bright) NK cells in treatment-naive HIV-1-seropositive individuals

Human immunodeficiency virus-1 (HIV-1) infected patients show a gradual loss of natural killer (NK) cells that correlates with disease progression. However, the effect of HIV-1 infection on different NK cell subsets has not been fully characterized. In healthy individuals most NK cells are CD3^–CD56⁺ and two different subpopulations, CD56^dim and CD56^bright, can be distinguished by the mean fluorescence intensity. Although it was originally suggested that CD56^bright NK cells represent the precursors of the CD56^dim subpopulation, recent cumulative data indicate that CD56^bright and CD56^dim NK cells are phenotypically, functionally, and developmentally different NK cell subsets. In this study, the analysis of CD56^bright and CD56^dim NK subsets showed that neither the number nor the phenotype of CD56^bright NK cells were significantly altered in treatment-naive HIV-1-infected individuals, whereas the number of CD56^dim NK cells was decreased. We also have studied NK cell subsets defined by the expression of CD56 in combination with CD16, CD161, or CD94 molecules. Our results demonstrated a preferential decrease of CD3^–CD56⁺ NK cells coexpressing CD16 and CD161 but lacking CD94 molecules. On the contrary an increased percentage of NK cells that do not express CD56 molecules but express CD16, CD161, or CD94 was also found in HIV-1-infected individuals. As it has been proposed that these CD56-negative NK cells expressing other NK cell receptors represent immature NK cells with low cytolytic capacity, our results support that a defective differentiation from immature CD56 negative NK cells to mature CD56^dim NK cells occurs in HIV-1 infection.