HIV-1感染者淋巴细胞活化与第二受体表达的研究

目的：了解HIV－1感染者体内淋巴细胞的活化情况及表达第二受体CCR5、CXCR4的淋巴细胞活化状态，分析这些指标与疾病严重程度的关系，探讨HIV感染的免疫基础。方法：用三色标记法流式细胞术检测24例HIV－1感染者及13例健康对照的抗凝血标本，分析活化标志物HLA－DR及第二受体CCR5、CXCR4的表达等指标。结果：HIV－1感染者CD8^ T淋巴细胞的HLA－DR表达高于健康对照（P＜0．001）；HIV－1感染者表达CCR5、CXCR4的CD8^ T淋巴细胞活化明显高于健康对照（P＜0．001）；表达CCR5CD4^ 、CD8^ T淋巴细胞与表达CXCR4相比HL－DR表达均明显增高（P＜0．001）；CD4^ 、CD8^ T淋巴细胞的活化状态与CD4百分率的变化明显关系。结论：HIV－1感染者CD8^ T淋巴细胞及表达不同第二受体的CD8^ T淋巴细胞活化程度明显增高，活化程度与疾病进程相关。     

HCV-RNA水平对HIV/HCV合并感染者HIV疾病进展影响研究

目的 探讨人免疫缺陷病毒(HIV)和丙型肝炎病毒(HCV)混合感染者HCV-RNA水平对HIV感染疾病进展的影响.方法 采用横断面研究对391例不同途径HIV感染者进行抗HCV-IgG、HCV-RNA、HIV-RNA、T淋巴细胞计数及其他免疫活化指标检测,比较HCV-RNA水平高组和低组病毒学及免疫学相关指标差别,分析HCV-RNA与HIV-RNA、CD4+T淋巴细胞计数的相关性.结果 (1)有偿供血组(93%)和静脉吸毒组(97.5%)抗HCV-IgG阳性率显著高于性接触组(20.1%);在抗HCV-IgG阳性的HIV感染者中,静脉吸毒组HCV-RNA阳性率(89.9%)显著高于有偿供血组(48.3%)及性接触组(62.5%),P均<0.01.(2) HCV-RNA水平和HIV-RNA水平正相关(r=0.237,P<0.01),与CD4计数负相关(r=-0.201,P<0.05).(3) HCV-RNA高组免疫活化标志物HLA-DR表达高于HCV-RNA低组(P<0.01).结论 高水平的HCV-RNA可能是HIV感染疾病进展的危险因素之一.     

HIV/AIDS患者NK细胞趋化因子受体表达研究

目的:探讨中国HIV/AIDS患者NK细胞表面趋化因子受体CXCR4、CCR5表达情况。方法:采用流式细胞仪分析HIV/AIDS患者外周血NK细胞表面趋化因子受体CCR5和CXCR4的表达。结果:未治疗典型HIV/AIDS患者NK细胞表面趋化因子受体CXCR4和CCR5与正常对照无显著差异(P >0 0 5 ) ,HIV长期不进展者NK细胞CCR5受体低于未治疗的典型HIV/AIDS患者(P <0 0 5 ) ,与正常对照相比无显著差异(P =0 0 5 ) ;HAART治疗组NK细胞趋化因子受体CCR5表达显著低于未治疗典型HIV/AIDS患者(P <0 0 1)。结论:趋化因子受体CCR5在NK细胞上表达的变化与疾病的不同阶段密切相连,对NK趋化因子受体的检测有助于艾滋病疾病进程的研究     

HCV与HIV混合感染研究进展

艾滋病病毒(HIV)与丙型肝炎病毒(HCV)感染是世界性的重要公共卫生问题,因二者存在相同的传播途径,其混合感染的发生率极高.HIV感染可导致免疫抑制,加速HCV发展为慢性肝病、肝硬化及原发性肝癌,同时HCV感染可加速HIV感染的疾病发展进程.从流行病学方面对HIV/HCV混合感染的作用特点、治疗方面进行综述,深入探讨HIV与HCV混合感染相互影响特点,为将来进行关于HIV和HCV混合感染研究提供方向.     

HCV与HIV混合感染研究进展

艾滋病病毒(HIV)与丙型肝炎病毒(HCV)感染是世界性的重要公共卫生问题,因二者存在相同的传播途径,其混合感染的发生率极高.HIV感染可导致免疫抑制,加速HCV发展为慢性肝病、肝硬化及原发性肝癌,同时HCV感染可加速HIV感染的疾病发展进程.从流行病学方面对HIV/HCV混合感染的作用特点、治疗方面进行综述,深入探讨HIV与HCV混合感染相互影响特点,为将来进行关于HIV和HCV混合感染研究提供方向.     

HIV/HCV共感染者自然杀伤细胞表面活化性与抑制性受体表达的研究

目的 比较HIV/HCV共感染、单纯HCV感染、单纯HIV感染者和健康人自然杀伤细胞（NK）数量及其表面受体的变化,了解HIV/HCV共感染者NK细胞表面活化性与抑制性受体表达特点.方法 采用流式细胞术对24例HIV/HCV共感染者,28例单纯HCV感染者,21例单纯HIV感染者外周血NK细胞数量与其表面活化与抑制性受体进行检测并与20例健康人进行比较分析.结果 HIV/HCV共感染组NK细胞绝对值较其他3组显著减少;共感染组、单纯HIV感染组、单纯HCV感染组NK细胞上NKP30和NKP46的表达频率都显著低于健康对照组,但NKP30的频率在前3组之间差异无统计学意义.共感染组和单纯HIV感染组的NKP46表达频率都显著低于HCV单纯感染组,而前2组之间差异无统计学意义;共感染组和单纯HCV感染组的NKG2A表达频率显著高于健康对照组和单纯HIV感染组,而前2组之间差异无统计学意义,但单纯HIV感染组NKG2A表达频率显著低于健康对照组;NK细胞NKG2D、CD158a和CD158b的表达频率在各组间差异无统计学意义.结论 HIV/HCV共感染者NK细胞绝对值明显降低,其表面活化性受体表达减少,某些抑制受体表达增加,甚至高于单纯HIV感染者,HIV/HCV共感染者NK细胞受损更加严重.     

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。     

HIV辅受体的研究进展

目前关于HIV辅助受体折研究已经成为一个研究热点，HIV辅助受体的发现以及HIV与辅助受体之间作用机制的深入研究。为防止HIV感染、治疗艾滋病提供了新的思路。本文旨在阐述目前HIV辅受体的研究进展。     

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。     

HIV／HCV共感染者NK细胞数量和功能的研究

目的 研究HIV/HCV共感染者的NK细胞数量和功能的变化,探讨HIV/HCV共感染对NK细胞的影响。方法 应用流式细胞术（FCM）检测HIV/HCV共感染者（n=18）、单纯HIV感染者（n=20）、单纯HCV感染者（n=30）及健康对照（n=18）的NK细胞数量,用PMA和K562细胞刺激外周血单个核细胞（PBMC）、流式细胞术检测NK细胞分泌IFN-γ的能力,并用流式细胞毒性分析法检测NK细胞对K562细胞的杀伤效率,对各组NK细胞的功能进行分析和比较。结果 HIV/HCV共感染者、单纯HIV感染者、单纯HCV感染者的NK细胞频率、NK细胞分泌IFN-γ的能力以及对K562细胞的杀伤能力都显著低于健康对照;HIV/HCV共感染者的NK细胞绝对值和对K562细胞杀伤能力显著低于HIV和HCV单纯感染者。结论 HIV/HCV共感染对NK细胞数量和功能的影响较单纯HIV和HCV感染更加严重。     

Mixed cryoglobulinemia in HCV mono-infected and HCV/HIV co-infected patients

The aim of our study was to compare the prevalence of mixed cryoglobulinemia in a group of HCV positive/HIV- negative patients with respect to a group of HCV/HIV co-infected subjects. Between September 2002 and May 2003, 58 patients with proven HCV infection and 67 subjects with HIV/HCV co-infection were enrolled. Serum was assessed for detectable cryoglobulins, liver enzymes, HCV viral load and HCV genotypes. In HIV positive patients, plasma HIV RNA and CD4+ cell count were determined. A chi-square test was used to compare the prevalence of cryoglobulins in our two categories of patients. Cryoglobulinemia was detected in 14/58 HCV mono-infected patients (24.1%) and in 10/67 HCV/HIV co-infected patients (14.9%), without any significant statistical difference between the two groups (p=0.2). Only two HCV mono-infected patients complained of arthralgia. No significant correlation was found between the presence of cryoglobulinemia and ALT levels, HCV viremia and duration of HCV infection. In HIV patients circulating cryoglobulins were not correlated with plasma HIV viral load, CD4 cell count and with duration of HIV infection. In conclusion, mixed cryoglobulinemia may be detected in a similar rate in the two groups and HIV infection does not appear to play a significant role in cryoglobulin production.     

The basal activation state of DC subsets correlates with anti-HCV treatment outcome in HCV/HIV co-infected patients

In this work we evaluated plasmacytoid (pDC) and myeloid dendritic (mDC) cells activation before and during anti-HCV treatment in HCV+/HIV+ individuals. HCV+/HIV+ patients received Peg-IFN-α2b subcutaneously for 28 days, followed by oral weight-based ribavirin. DCs activation was evaluated by flow cytometry. Baseline pDC CD80 and CD86 expression was correlated with HIV, but not with HCV viral load. A transient decrease of HIV RNA was found not associated with DC activation. When patients were grouped according to early/sustained virological response (EVR/SVR) to anti-HCV treatment, baseline pDC CD80 and CD86 expression was higher in non-EVR and non-SVR compared to EVR and SVR. Moreover, in responder patients CD80 and CD86 were upregulated by IFN-α. Our data suggest a correlation between DCs activation and response to therapy. These findings could be helpful to better understand the mediators of IFN-α action in HCV+/HIV+ patients and to explore possible exploitation of this knowledge to improve therapeutic response.     

Antibody and markers of T-cell activation illuminate the pathogenesis of HCV immune restoration disease in HIV/HCV co-infected patients commencing ART

Some HIV/hepatitis C virus co-infected patients beginning ART experience Immune Restoration Disease (IRD) manifested as a rise in serum alanine transaminase. This was investigated in HIV/HCV co-infected individuals (n=50) commencing ART in Jakarta (Indonesia). Samples were collected at weeks 0, 4, 8, 12, 24 and at HCV IRD. Nine patients experienced HCV IRD (incidence=9.2 per 1000 person-weeks). These resolved without changing treatment. Markers of T-cell activation (sCD26, sCD30) and immune recruitment (CXCL10) increased in many HCV IRD cases, so T-cells may mediate HCV IRD. Total anti-HCV antibody (core, NS3, NS4) remained lower in HCV IRD cases, but levels of antibody to core were not lower in HCV IRD cases. Rises in HCV RNA on ART were independent of HCV IRD, but there was a negative correlation between baseline HCV RNA and total anti-HCV antibody. High levels of antibody may protect against HCV IRD, via lower HCV antigen loads.     

Non-invasive markers of liver fibrosis in HCV mono-infected and in HIV/HCV co-infected subjects

Non-invasive markers of liver fibrosis have been recently developed as a possible alternative to liver biopsy. The clinical management of hepatic diseases is dependent on the extent of liver fibrosis. Liver biopsy remains the gold standard but severe complications are found in about 0.5% of cases. Studies involving sequential liver biopsies are impractical, costly, and risky. Therefore non-invasive markers of liver fibrosis could be useful. These drawbacks justify an intensive research on non-invasive alternatives. Several serum markers are either directly involved in fibrosis remodelling or are indirectly associated with the presence of significant liver fibrosis. More recently, fibrosis scores calculated from statistical models have been described. This review describes the role of non-invasive markers in assessing hepatic fibrosis in both HCV mono-infected and HIV/HCV co-infected subjects.     

Reciprocal influence of HIV and HCV infections in co-infected patients and the involvement of HAART

The reciprocal influence of HIV-HCV co-infection was established prior to the era of highly active retroviral therapy (HAART) and continues to be a topic of debate, including the question of which infection to treat first.     

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection

Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads < 10,000 copies/ml, CD4(+) count > 250/microl. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r = 0.47; P = 0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4(+), HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r = 0.52; P = 0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P = 0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P = 0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration.     

HCV in peripheral blood mononuclear cells are predominantly carried on the surface of cells in HIV/HCV co-infected individuals

HCV replication in extra-hepatic reservoirs has been suggested to occur in many tissues including PBMCs. A recent study showed evidence for compartmentalization and evolution of HCV in PBMCs. However, the cells that support HCV replication in PBMCs have not been identified. In this study we have fractionated the PBMC from HIV/HCV co-infected patients into T, monocytes, B and NK cells, and most of the HCV was located in CD3-cell fractions. Protease treatment of PBMCs to remove cell surface receptors resulted in the loss of HCV RNA suggesting that most of the HCV is present on the cell surface. PBMCs were treated by freeze-thaw nuclease method that would protect the HCV RNA in the virus but not the intracellular viral RNA. Data from this analysis support the conclusion that most of HCV is present on the cell surface. Even though the presence of minus strand RNA in PBMCs suggests that a low level HCV replication takes place within the PBMCs of HIV/HCV co-infected individuals, HCV in PBMC is present mainly on the surface of non-T cells, mostly on NK, monocytes and B cells. These results suggest a unique pathogenic role of NK, monocyte and B cells as carriers of HCV.