HIV／AIDS患者血浆病毒载量及外周血T淋巴细胞亚群的变化

目的：观察国内HIV／AIDS患者血浆病毒载量和外周血CD4^ 、CD8^ T淋巴细胞的变化，探讨这些变化的临床意义。方法：选择未经抗病毒治疗的HIV／AIDS患者124例，用bDNA法检测血浆病毒载量，并用流式细胞仪检测外周血CD4^ 、CD8^ T淋巴细胞。结果：AIDS患者的血浆病毒载量明显高于HIV感染者，血浆病毒载量与CD4^ 细胞计数呈显著负相关，但其最高峰位于CD4^ 细胞计数100／μl处，然后随着CD4^ 细胞计数的下降而减少。CD4^ T细胞计数为AIDS组＜HIV组＜正常对照组：HIV感染者的CD8^ T细胞计数显著高于正常组和AIDS组，而AIDS患者CD8^ T细胞数则随着CD4^ T细胞减少而下降。结论：血浆病毒载量随着疾病进展而显著升高，但在疾病晚期则有所降低。外周血CD4^ T细胞计数随着疾病的进展而进行性减少；CD8^ T细胞计数在感染早期显著升高，进入晚期则减少。在评价HIV感染者和AIDS患者病情时，应结合病毒载量、CD4^ 、CD8^ T细胞计数综合分析。     

HIV感染者/AIDS患者外周血CD38 HLA-DR分子在CD4+ CD8+T淋巴细胞上的表达

目的　观察国内艾滋病病毒 (HIV)感染者 /艾滋病 (AIDS)患者外周血CD38、HLA DR分子在CD+4 、CD+8T淋巴细胞上表达的变化 ,并探讨这些变化的临床意义。方法　用流式细胞仪检测 5 1例正常对照、14例HIV感染者和 3 6例AIDS患者的外周血CD+4 、CD+8T淋巴细胞表面的CD38、HLA DR分子的表达 ,用分枝DNA(bDNA)法检测 11例HIV感染者和 18例AIDS患者的血浆病毒载量。结果　CD+4 HLA DR+细胞百分比显示 ,AIDS组显著高于正常组及HIV组 ;CD+8HLA DR+T细胞百分比显示HIV组与AIDS组间无差异 ,而它们均显著高于正常组。CD+8、CD38+细胞百分比则是AIDS组 >HIV组 >正常组 ,CD+8CD38+、CD+8HLA DR+、CD+4 HLA DR+细胞百分比与病毒载量显著正相关。结论　在HIV感染过程中 ,HLA -DR+、CD38+在CD+4 、CD+8T淋巴细胞上的表达均显著增加 ,反映T淋巴细胞异常激活 ;尤其是CD+8CD38+细胞百分比随着疾病进展逐渐升高 ,预示疾病进展程度。在评价HIV感染者和AIDS患者的免疫状况时 ,不仅要考虑免疫细胞数量和功能的变化 ,还应考虑免疫细胞的激活水平     

HIV和HCV重迭感染者病毒载量间及与T淋巴细胞计数的相关性研究

目的探讨艾滋病病毒(HIV)和丙型肝炎病毒(HCV)重迭感染者两病毒载量间及其与T淋巴细胞计数的相关性。方法采用流式细胞技术和荧光定量PCR技术，对15例HIV和FICV重迭感染者进行了CD3^ 、CD4^ 、CD8^ 淋巴细胞计数和病毒核酸载量测定，并选用多种数学模型进行相关性分析。结果单因素相关回归分析显示：HIV病毒载量与CD3^ 和CD4^ 细胞计数分别呈现良好的负相关关系(r=-0．6013，P=0．0177；r=-0．8828，P=0．0000)，HCV病毒载量与CD3^ 和CD4^ 细胞计数分别呈现良好的正相关关系(r=0．5931，P=0．0198；r=0．8627，P=0．0000)，HIV和HCV病毒载量间存在统计学负相关关系(r=-0．8954，P=0．0000)。多因素线性相关回归分析表明：CD3^ 和CD4^ 细胞计数及HCV病毒载量与HIV病毒载量间均呈现良好的统计学负相关关系(r=-0．6051，P=0．0169；r=-0．8828，P=0．0000；r=-0．8954，P=0．0000)。逐步回归分析显示：CD4^ 细胞计数和CD4^ ／CD8^ 比值及HCV病毒载量与HIV病毒载量间分别存在统计学负相关关系。结论HIV／HCV重迭感染时．两病毒间表现出竞争性抑制或干扰现象．导致CD4^ 细胞计数多样化改变并呈现出下降趋势。     

HIV／AIDS患者和正常人T淋巴细胞亚群、表型及其相关性的比较研究

目的:探讨HIV／AIDS患者T淋巴细胞亚群、表型和CD4凋亡细胞之间的相关性及其临床意义。方法：用流式细胞仪法对HIV／AIDS患者和年龄相配的HIV阴性人群的T淋巴细胞亚群、表型和CD4凋亡细胞的绝对和相对计数进行测定，比较这些指标在两组人群中的差别和分析各项指标之间相关性。结果：在HIV／AIDS患者组，CD25细胞表型与CD4计数呈正相关，HLA－DR细胞表型的绝对计数也与CD4计数呈正相关，但其百分率却与后者无相关性。与对照组比较，患者组的CD4和CD25双阳细胞（CD4^ 、CD25^ ）百分率降低而总体HLA－DR水平升高。在患者组CD4细胞凋亡百分率与CD4计数呈负相关。结论：与CD4计数和百分率以及CD4用CD8的比值结结合，CD25水平有助于判断HIV感染的进程和判断疗效。CD4细胞凋亡可能有助于判断晚期艾滋病。     

安徽省HIV／AIDS儿童的免疫学及病毒学现况调查

目的全面了解和掌握安徽省感染艾滋病病毒／艾滋病（HIV／AIDS）儿童的免疫学及病毒学状况。方法对2007年安徽省HIV／AIDS儿童进行病史调查,并检测CD4、CD8细胞计数和CD4／CD8比值以及病毒载量。结果安徽省HIV／AIDS儿童的传播途径以母婴传播为主,治疗组和未治疗组儿童病毒载量的对数值存在统计学差异（P〈0．01）,治疗组62．5％的儿童病毒载量低于最低检出限,未治疗组儿童病毒载量均高于最高检出限。母婴传播感染HIV／AIDS儿童的感染时间与CD4细胞计数和病毒载量水平呈反向相关关系（P〈0．05）,CD8细胞计数与CD4细胞计数呈正向回归关系（r=0．553）,病毒载量对数值与CD4细胞计数呈反向回归关系（r=0．273）。结论安徽省HIV／AIDS儿童以母婴传播为主,抗病毒药物能有效抑制HIV的增殖。     

HIV／AIDS合并结核病177例临床分析

目的了解HIV／AIDS合并结核病（TB）的临床特点。方法对2003年06月-2007年12月我院177例HIV／AIDS合并TB住院患者的资料进行回顾性分析。结果177例患者中，男113例，女64例，年龄（39．8±11．5）岁。死亡31例（17．5％）。TB病原学检测总阳性率为30．5％。89例接受高效抗反转录病毒治疗患者中，治疗后CD4＋T淋巴细胞计数〉200／mm^3的30例（33．7％），CD4＋T淋巴细胞计数〈200／mm^3的59例（663％），6．7％发生免疫重建炎性综合征。有基线CD4＋T淋巴细胞计数检测的150例患者中，基线CD4^3T淋巴细胞计数〈50／mm^3占55．3％，CD4＋T淋巴细胞计数50～200／mm^3占36．7％，CD4＋T淋巴细胞计数〉200／mm^3占8．O％。结论HIV／AIDS合并TB患者比单纯的TB患者发生活动性TB的危险性增加；HIV／AIDS合并TB患者已经进入AIDS期，免疫功能低下，合并多重机会感染，病死率较高；但TB相关的实验室检查指标阳性率低，诊断困难。     

肝硬化患者外周血及腹水T淋巴细胞亚群的变化及意义

目的研究肝硬化患者外周血及腹水T淋巴细胞亚群的变化及意义。方法流式细胞仪测定31例肝炎后肝硬化患者外周血及腹水T淋巴细胞亚群，同时检测15例正常人的外周血T淋巴细胞亚群。结果肝硬化患者外周血T淋巴细胞（CD3^＋）、T辅助／诱导细胞亚群（CD4^＋）、T辅助淋巴细胞／T抑制淋巴细胞亚群（CD4^＋／CD8^＋）较正常对照明显降低（p＜0．01），腹水CD3^＋、CIM^＋、CD8^＋、CD4^＋／CD8^＋较外周血显著降低（P＜0．001）。结论肝硬化患者外周血及腹水T淋巴细胞亚群存在明显异常，表现为全身及腹膜腔局部的免疫力低下。     

人类免疫缺陷病毒感染者及艾滋病患者CD8~ CD38~ CD8~ HLA-DR 比例与HIV载量的相关性研究

目的研究人类免疫缺陷病毒(HIV)感染者和获得性免疫缺陷综合征(AIDS,艾滋病)患者CD8 T细胞激活分子CD38、人类白细胞Ⅱ类抗原(HLA-DR)与血浆HIV载量的相关性,分析用CD8 CD38 、CD8 HLA-DR 的比例替代HIV载量的可行性。方法采集1998—2006年期间在北京协和医院初诊的HIV感染者或AIDS患者236例和56名同期健康献血员的抗凝静脉血,用流式细胞术分析CD8 T细胞分别表达CD38和HLA-DR的比例,用分支DNA技术(bDNA)检测血浆病毒载量(VL)。用受试者工作特征曲线(ROC)分别预测VL>1×103拷贝/mL、>1×104拷贝/mL和>1×105拷贝/mL时CD8 CD38 、CD8 HLA-DR 比例的临界值范围。结果236例患者的CD4 T细胞计数138(16,262)×106/L,显著低于对照组(P<0.01);CD8 T细胞计数618(353,879),显著高于对照组(P<0.05);CD8 CD38 、CD8 HLA-DR 的比例分别为85.4%(72.5%,92.2%)和40.3%(17.5%,59.7%),显著高于对照组(P<0.01),与HIV载量的相关性分别为0.429(P<0.01)和0.282(P<0.01)。用CD8 CD38 >80.4%预测VL>1×103拷贝/mL的敏感度和特异度为80.6%和75.0%;用CD8 HLA-DR 预测VL>1×105拷贝/mL的敏感度和特异度为78.7%和81.4%。结论对HIV感染或AIDS初诊的患者可以尝试用CD38和HLA-DR激活亚群来预测血浆HIV载量,这种替代检测方法具有一定的可行性。     

HIV感染者/AIDS患者血清基质金属蛋白酶-9表达与T细胞亚群的相关性研究

目的：了解艾滋病病毒(HIV)感染者及艾滋病(AIDS)患者血清中基质金属蛋白酶—9(MMP—9)水平表达及与T细胞亚群的相关性。方法：用酶联免疫吸附试验(ELISA)和流式细胞分析法，检测了18例HIV感染者和24例AIDS患者血清中MMP—9水平和淋巴细胞中CD3^ 、CD4^ 、CD9^ 的表达及绝对数。结果：HIV感染者组和AIDS患者组MMP—9水平较对照组明显升高(P＜0．05，P＜0.01)。AIDS患者组CD3^ 细胞数较对照组显著减少(P＜0．05)。HIV感染者组和AIDS患者组CD4^ 计数降低非常明显(P＜0．001)，CD8^ 计数非常明显升高(P＜0．00l，P＜0．01)，CD4^ ／CD8^ 的比值倒置。AIDS患者组MMP—9水平、CD3^ ，CD4^ 、CD8^ 的表达较HIV感染者组均有明显差异。HIV感染者组和AIDS患者组MMP—9表达与CD4^ 细胞数呈负相关(P＜0．05，P＜0．01)，AIDS患者组MMP—9水平与CD8^ 细胞数明显相关(P＜0．05)。结论:感染HIV后，MMP—9的水平随病情发展而增加，CD3^ 、CD4^ 细胞数逐渐减少，可作为判断AIDS患者疾病严重程度的指标。     

艾滋病合并结核杆菌感染临床特征与T细胞亚群的相关性分析

目的 探讨艾滋病（AIDS）合并结核杆菌（TB）感染临床表现为肺结核、淋巴结结核时，患者T淋巴细胞亚群计数的差异及意义。方法 33例AIDS合并TB感染患者，临床表现分别为肺结核、淋巴结结核、肺结核与淋巴结结核并存，分别检测其T淋巴细胞亚群水平并进行两两比较。结果 不同临床表现患者CD3^＋、CD8^＋、CD4^＋T淋巴细胞计数比较均有明显差异，肺结核患者明显高于淋巴结结核患者（P〈0.01）。结论 AIDS合并TB感染患者临床特征与其T淋巴细胞亚群计数相关。     

正常T细胞分泌激活因子基因多态性与HIV-1感染者病毒载量、CD+4细胞计数和CD+4/CD+8比值的关系

目的分析正常T细胞分泌激活因子(RANTES)启动子和内含子等位基因,对艾滋病病毒1型(HIV-1)感染者外周血CD+4细胞计数、CD+4/CD+8比值和病毒载量的关系,以期探讨RANTES单核苷酸多态性(SNP)和艾滋病(AIDS)发病的关系.方法用流式细胞仪和real time法对40例汉族HIV-1感染者测定外周血CD+4、CD+8细胞计数和病毒载量,应用PCR-RFLP法进行基因分型.结果对RANTES-403、-28和In1.1三个位点等位基因与外周血CD+4T淋巴细胞计数、CD+4/CD+8+比值和病毒载量的关系的分析表明,具有RANTESIn1.1 C/C和T/C基因型的感染者,与较高的病毒载量、较低的C+4T细胞计数和C+4/CD+8比值有关.In1.1 T/T与T/C、C/C基因型的log10病毒载量的差异有非常显著的统计学意义(P＜0.01),但是不同基因型之间CD+4T淋巴细胞计数和CD+4/CD+8细胞比值则无显著性差异.log10病毒载量和CD+4T淋巴细胞计数(r=-0.447,P＜0.01)、CD+4/CD+8比值(r=-0.369,P＜0.05)有显著的负相关关系.结论所研究人群中,具有RANTES In1.1C的基因型者,与较高的病毒载量、较低的CD+4T细胞计数和CD+4/CD8+比值有关,它们是反映AIDS进程的主要指标,可能加速AIDS发病进程;而RANTES-403和-28等位基因的影响则处于相对次要的作用.     

Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users

OBJECTIVE: To identify subsets of CD4 T lymphocytes that can predict the development of AIDS and to assess whether increased levels of these cellular markers could provide additional independent prognostic information to the CD4 T cell count and plasma HIV-1-RNA levels. DESIGN AND METHODS: In a prospective study, a cohort of 85 HIV-positive intravenous drug users [clinical categories of the CDC classification A (n = 48) and B (n = 37)] were followed for a period of 37+/-13 months. Memory and activated CD4 and CD8 T cells were quantitated by three-colour flow cytometry at baseline and expressed as a percentage of total CD4 and CD8 lymphocytes. Clinical evaluations were performed at 6 month intervals. The relationships between these lymphocyte subsets and progression to AIDS were studied using Kaplan-Meier plots and proportional hazards regression models. RESULTS: After adjustment for the level of CD4 T cells and plasma HIV-1-RNA levels, the elevation in the subset CD4+CD38+DR+ was the marker within the functionally distinct subsets of CD4 T lymphocytes with additional prognostic value in bivariate Cox regression models. In multivariate models, increased percentages of CD4+CD38+DR+ T cells provided the strongest independent prognostic information for progression to AIDS (relative hazard, 1.07; P < 0.0001). CONCLUSION: Our results suggest that high levels of CD4+CD38+HLA-DR+ T cells reflect the increasing degree of CD4 T cell activation during the progression of HIV infection, and could be used together with the CD4 T cell and HIV-RNA levels to evaluate more accurately the progressive cellular immune impairment associated with the risk of progression to AIDS.     

Relationship of frequency of CD4+CD25+Foxp3+ regulatory T cells with disease progression in antiretroviral-naive HIV-1 infected Chinese

Forty-five antiretroviral-naive HIV-1 infected patients and 14 healthy controls in North China were enrolled in this study. The frequency of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and levels of expression of CD95, HLA-DR and CD38 in T cells were detected by flow cytometry. We found that the frequency of Tregs was higher in AIDS patients than in asymptomatic HIV-1 infected patients (P=0.004). The frequency of Tregs was significantly correlated with absolute CD4 count, viral load, CD4+CD95+ T cells and CD8+CD95+ T cells (P<0.05). The relationship between the frequency of Tregs and immune activation was not found in HIV-infected patients. We concluded that the frequency of Tregs in HIV-infected Chinese patients was significantly correlated with disease progression.     

CD+8 T细胞激活分子CD38、HLA-DR与HIV-1载量的相关性研究

目的研究HIV/AIDS患者CD8^＋ T细胞表达激活分子CD38、HLA-DR水平与血浆病毒载量（VL）的相关性,以及用CD8CD38、CD8HLA-DR比例替代VL检测的可行性.方法用流式细胞术分析103例接受12个月高效抗逆转录病毒治疗（HAART）患者的CD＋8 T细胞表达CD38和HLA-DR水平;用分支DNA扩增技术检测血浆VL.用敏感性、特异性、准确性等参数分析能有效预测VL＜50拷贝/ml、VL＜500拷贝/ml、VL＞1000拷贝/ml和VL＞10 000拷贝/ml时CD8CD38和CD8HLA-DR的检测范围.结果103例艾滋病患者CD38、HLA-DR和VL在12个月治疗中均呈下降趋势;CD38和VL在HAART治疗前及治疗第1、3、6、9、12个月6个检测点的总相关系数为0.483（P＜0.001）、HLA-DR和VL的总相关系数为0.477（P＜0.001）.用CD8CD38和CD8HLA-DR的水平预测VL值有显著诊断价值：当CD38＜68.5%和＜72.5%时预测VL＜50拷贝/ml和＜500拷贝/ml有较高的灵敏度和特异性;当HLA-DR在＞39.5%和＞46.5%时预测VL＞1000拷贝/ml和＞10 000拷贝/ml有较高的灵敏度和特异性.结论在条件匮乏的艾滋病高发区,可以用CD8CD38和CD8HLA-DR激活亚群的结果来预测血浆VL,作为监测HIV疾病进展和评价抗病毒疗效的参考.     

Expansion of CD57 and CD62L-CD45RA+ CD8 T lymphocytes correlates with reduced viral plasma RNA after primary HIV infection.

OBJECTIVE: CD8 T cells, expressing cell surface molecules distinct from those on resting and naive T cells, are increased in HIV infection. The association of increased CD38 and human leukocyte antigen DR (HLA-DR) CD8 T cells with poor prognosis has suggested that activated CD8 T cells may aggravate HIV infection. We examined whether other immunological parameters might influence the viral setpoint. DESIGN: Peripheral T cells from nine untreated patients, obtained after primary HIV infection when plasma HIV had stabilized, were examined for proteins expressed in activated versus resting, memory versus naive, and cytolytic versus non-cytolytic T cells. METHODS: The proportion of CD8 T cells that stain for CD38 and HLA-DR, CD28 and CD57 was compared with plasma viraemia and CD4 cell count. These parameters were also compared with the proportion of CD4 and CD8 T cells that express CD62L and CD45RA, present on naive cells and down-modulated in memory cells. Internal staining for the cytotoxic protein granzyme A was also examined. RESULTS: An increase in CD38 and CD38 HLA-DR CD8 T cells correlated with increased plasma viral RNA (P < 0.00002, P < 0.03, respectively). An increase in CD8 T cells expressing granzyme A was associated with lower CD4 cell counts (P < 0.04). However, the expansion of CD57 and CD62L CD45RA+ CD8 T cells was associated with a lower viral setpoint (P < 0.01, P < 0.02, respectively). CONCLUSION: Phenotypically defined activated CD8 T cells may have different functions in HIV infection. Activated CD8 T cells that are CD57 or CD62L(-)CD45RA+ may be beneficial, because their expansion in untreated patients correlates with a reduced viral setpoint after primary infection.     

HIV-1感染者CD73~+CD8~+ T细胞减少与T细胞异常活化的相关性研究

目的探讨HIV-1感染者外周血CD8~+T细胞上CD73的表达特点及其与T细胞异常活化和疾病进展的关系。方法研究入选65例HIV-1感染者和27例健康对照。通过流式细胞术检测研究对象外周血CD73~+CD8~+T细胞的频率和绝对计数,并将患者CD73~+CD8~+T细胞绝对计数和频率与其CD4~+T细胞计数、HIV-1载量以及CD38~+CD8~+T细胞频率进行相关性分析。结果与健康对照相比,HIV-1感染者外周血CD73~+CD8~+T细胞绝对计数和频率均明显降低(P均0.05);HIV-1感染者外周血CD73~+CD8~+T细胞绝对计数和频率与CD4~+T细胞计数呈正相关(r=0.555,P=0.001;r=0.342,P=0.005),与CD38~+CD8~+T细胞频率呈负相关(r=-0.384,P=0.002;r=-0.387,P=0.001);HIV-1感染者CD73~+CD8~+T细胞的绝对计数与HIV-1载量呈弱负相关(r=-0.261,P=0.035)。结论 HIV-1感染者外周血CD73~+CD8~+T细胞的减少不但与患者T细胞的活化程度呈显著负相关,而且与AIDS疾病进展相关。     

Immunophenotype of HIV+ patients during CD4 cell-monitored treatment interruption: role of the IL-7/IL-7 receptor system

OBJECTIVE: To investigate immunological changes during CD4-guided therapy interruption in HIV(+) patients who suspended HAART. PATIENTS: Seventeen patients aged > 18 years, who had received HAART for at least 12 months, and had a pre-interruption CD4+ cell count > 500 cells/microl, interrupted treatment. Median nadir CD4(+) cell count was 288 cells/microl. HIV plasma viral load at discontinuation was < 50 or > 50 copies/ml. Criteria for restarting treatment were: a CD4(+) T-lymphocyte count < 350 cells/microl on two separate occasions, a clinical manifestation of AIDS, and the patient's desire to resume HAART. Eleven patients were still off therapy after 12 months (group A); according to the first criterion, six patients restarted therapy within 12 months (group B). METHODS: Haematological, viro-immunological, cytofluorimetic and molecular assays were performed at baseline and every 2 months following standard methods. Statistical analysis was performed under Stata 7.0. RESULTS: In the first 2 months of treatment interruption, a significant increase in viral load and CD8(+) lymphocyte activation occurred. Then such parameters decreased and remained stable. In all patients, a decrease in CD4(+) lymphocytes took place as well, that affected in a similar manner naive, central memory, effector memory and terminally differentiated cells. Group B always presented lower amounts of CD4(+) effector memory lymphocytes. The expression of CD127 was always higher in group A. CONCLUSIONS: The loss of CD4(+) lymphocytes upon viral rebound is equal among naive and memory subsets. Patients with higher expression of CD127, who are likely to exert a better capacity to utilize endogenous interleukin-7 by T cells, could remain off therapy for longer periods.     

T cell activation in HIV-seropositive Ugandans: differential associations with viral load, CD4+ T cell depletion, and coinfection

Immune activation is thought to play a major role in the pathogenesis of human immunodeficiency virus (HIV). This effect may be particularly relevant in Africa, where endemic coinfections may contribute to disease progression, perhaps as a consequence of enhanced immune activation. We investigated the expression of CD38 and human leukocyte antigen (HLA)-DR on T cells in 168 HIV-seropositive volunteers in Uganda. We observed higher levels of CD4(+) and CD8(+) T cell activation in Uganda, compared with those reported in previous studies from Western countries. Coexpression of CD38 and HLA-DR on both CD4(+) and CD8(+) T cell subsets was directly correlated with viral load and inversely correlated with CD4(+) T cell counts. In antiretroviral therapy (ART)-naive volunteers, viral load and CD4(+) T cell count had stronger associations with CD8(+) and CD4(+) T cell activation, respectively. Virus suppression by ART was associated with a reduction in T cell activation, with a stronger observed effect on reducing CD8(+) compared with CD4(+) T cell activation. The presence of coinfection was associated with increased CD4(+) T cell activation but, interestingly, not with increased CD8(+) T cell activation. Our results suggest that distinct mechanisms differentially drive activation in CD4(+) and CD8(+) T cell subsets, which may impact the clinical prognostic values of T cell activation in HIV infection.