艾滋病实验室检测进展（文献综述）

获得性免疫缺陷综合征(acqlliDed immunodeficiency syn-arome)简称艾滋病(AIDS),是由人类免疫缺陷病毒(humanimmunodeficiency virus,HTV)感染所引起的一种严重的传染性疾病.自1985年第一代HIV/抗体问世以来,HIV病原学检测方法有了长足的进步.     

艾滋病发病学研究进展与药物和疫苗研发新策略

在人类历史上,艾滋病(acquired immunodefi-ciency syndromes,AIDS)是最为严重的传染病,这体现在它既是一种流行范围极广的疾病,又是一种死亡率极高的疾病[1].HIV病(human immunodeficien-ey virus disease,HIV disease)指从H1V感染到AIDS发病的整个病程.     

艾滋病患者心理状态分析及对策

<正>山西省艾滋病定点收治单位先后收治人免疫缺陷病毒(HIV)感染者/获得性免疫缺陷综合征(AIDS)患者55例,针对他们存在的心理问题及其特点进行干预和治疗效果明显,现报告如下。1HIV感染者/AIDS患者负性心理分析1.1疾病本身:一旦感染HIV,感染者就会产生比患任何疾病都严重、复杂的心理障碍,这种负性情绪一方面来自HIV/     

HIV感染的实验室诊断研究进展(文献综述)

获得性免疫缺陷综合征(Acquired immunodeficiency syndrome),简称艾滋病(AIDS).是由人类免疫缺陷病毒(HIV)感染引起的一种全身性疾病.自首例病例发现以来,在短短的二十几年间,全球已有4000万人感染HIV,其中300万人被艾滋病夺去生命[1].我国自1985年发现首例艾滋病病例后,AIDS的流行也呈加速发展趋势.据报道[2～3],我国HIV感染已近100万人,若不采取有效控制措施,到2010年我国HIV感染将达到1000万人,形势十分严峻[4～6].HIV感染的实验室诊断是艾滋病预防控制工作的重要组成部分,只有发现传染源才能有效控制艾滋病的传播.     

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     

中国HIV感染长期不进展者T细胞表面IL-7受体表达研究

目的:了解中国HIV感染长期不进展者(Long-Term Non-Progressor,LTNP)T细胞表面IL-7(Interleukin-7,IL-7)受体的表达,分析其与疾病进展的关系。方法:收集LTNP组、HIV组、AIDS组及健康对照组(每组各20例)的抗凝全血,用流式细胞仪检测IL-7受体的表达,并分析IL-7受体表达与血浆中IL-7水平的相关性。结果:LTNP组CD4+T、CD8+T、中枢记忆T细胞(Central memory T cells,Tcm)、效应记忆性T细胞(Effector memory T cells,Tem)表面IL-7受体表达水平明显高于无症状HIV感染组(HIV组)、AIDS病人组(AIDS组)(P<0.05),LTNP组初始T细胞(Na ve T cells,Na ve)、终末分化效应记忆型T细胞(Terminallydifferentiated effector memory T cells,Tem/td)表面IL-7受体表达水平与HIV组、AIDS组间差异无统计学意义。HIV/AIDS患者IL-7受体在CD4+T和CD8+T细胞上表达的百分率与血浆IL-7水平呈明显负相关(P<0.05),与CD4+T细胞数量呈明显的正相关(P<0.05),与病毒载量呈明显负相关(P<0.05)。结论:外周血T细胞表面IL-7受体表达与HIV疾病进展密切相关,LTNP组T细胞保持较高水平的IL-7受体表达,可能是保护因素之一。     

HIV感染病人的血清学诊断及结果分析

获得性免疫缺陷综合征(AIDS)是由艾滋病病毒(HIV)引起的一种全身性疾病.我国自1985年发现第一例艾滋病以来,病例数逐年上升.据报道[1],目前我国有艾滋病病毒(HIV)感染者84万例,其中艾滋病病人8万例.已引起我国政府和卫生防疫部门的高度重视.HIV感染的诊断是艾滋病预防控制工作的重要组成部分,只有发现传染源才能有效控制艾滋病传播.     

硒与HIV感染的关系研究进展

HIV感染及AIDS至今依然严肃威胁人类的生命，因而成为医学界研究的热点，本文着重从硒与细胞因子角度揭示硒与HIV和AIDS在发生、发展中的关系。证明其扮演的重要角色，提示了一种研究HIV和AIDS的新方向。     

外周血纯真、记忆性CD8~+T细胞数量与中国HIV/AIDS患者疾病进程的相关性研究

目的:研究不同疾病进展阶段的中国HIV/AIDS患者外周血CD8+T细胞亚群的数量变化,以探讨各亚群与HIV感染疾病进展的相关性。方法:首先应用多参数(CD45RA、CCR7、CD28)流式细胞术圈定幼稚(nave)CD8+T细胞和记忆性(memory)CD8+T细胞(包括TCM、TEM-1及TEM-2),随后测定58例不同疾病进展阶段HIV/AIDS患者和20例健康对照者外周血各CD8+T细胞亚群的绝对数量和占CD8+T细胞的百分比,分析其与病毒载量、CD4+T细胞数量的相关性。结果:HIV/AIDS患者与健康对照相比,nave CD8+T细胞百分比和绝对值均显著减少,memory CD8+T细胞百分比和绝对值均显著升高(P0.05)。在memoryCD8+T细胞各亚群中,效应型(effector memory T cells,TEM)-1百分比显著升高(P0.05)。HIV感染缓慢进展(slow progressor,SP)组、HIV组及AIDS组中,nave CD8+T细胞百分比和绝对值均依次下降,AIDS组、HIV组显著低于SP组(P0.05),memory CD8+T细胞绝对值依次下降,各组间的下降均有显著性差异(P0.05)。在memory CD8+T细胞各亚群中,TEM-1百分比依次升高,AIDS组显著高于SP组(P0.05);TEM-2百分比及绝对值依次下降,AIDS组显著低于SP组(P0.05)。相关性分析发现,nave CD8+T细胞与CD4+T细胞显著正相关(P0.01),与HIV病毒载量显著负相关(P0.01);中央型(central memory T cells,TCM)和TEM-2型memory CD8+T细胞与CD4+T细胞显著正相关(P0.01)。结论:Nave、memory CD8+T细胞数量与HIV疾病进展显著相关。     

检测HIV早期感染的血清学方法

艾滋病，即获得性免疫缺陷综合征（AIDS）是由人类免疫缺陷病毒（HIV）引起的一种免疫缺陷性疾病。世界范围内AIDS预防控制工作的首要任务在于识别出早期感染的人群（新发感染人群），进而估计HIV的发病率，掌握HIV感染的变化趋势，同时对早期感染人群进行干预和有效控制，以遏制HIV的蔓延趋势。     

Monitoring α4β7 integrin expression on circulating CD4+ T cells as a surrogate marker for tracking intestinal CD4+ T-cell loss in SIV infection

Intestinal CD4+ T cells are rapidly and profoundly depleted in human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV)-infected macaques. However, monitoring intestinal cells in humans is difficult, and identifying surrogate markers in the blood, which correlate with loss or restoration of intestinal CD4+ T cells could be helpful in monitoring the success of therapeutic strategies and vaccine candidates. Recent studies indicate HIV utilizes the intestinal homing molecule α4β7 for attachment and signaling of CD4+ T cells, suggesting this molecule may have a central role in HIV pathogenesis. Here, we compared β7^HIGH integrin expression on CD4+ T cells in blood with loss of CD4+ T cells in the intestine of macaques throughout SIV infection. The loss of β7^HIGH CD4+ T cells in blood closely paralleled the loss of intestinal CD4+ T cells, and proved to be a more reliable marker of intestinal CD4+ T-cell loss than monitoring CCR5+ memory CD4+ T cells. These data are consistent with a recent hypothesis that α4β7 has a role in the selective depletion of intestinal CD4+ T cells, and indicate that monitoring β7^HIGH expression on CD4+ T cells in the blood may be a useful surrogate for estimating intestinal CD4+ T cell loss and restoration in HIV-infected patients.     

Purinergic signaling and human immunodeficiency virus/acquired immune deficiency syndrome: From viral entry to therapy

Human immunodeficiency virus(HIV) infection is a serious condition associated to severe immune dysfunction and immunodeficiency. Mechanisms involved in HIV-associated immune activation, inflammation and loss of CD4+ T cells have been extensively studied, including those concerning purinergic signaling pathways. Purinergic signaling components are involved in viral entry and replication and disease progression. Research involving the participation of purinergic signaling in HIV infection has been not only important to elucidate disease mechanisms but also to introduce new approaches to therapy. The involvement of purinergic signaling in the pathogenesis of HIV infection and its implications in the control of the HIV infection are reviewed in this paper.     

Presence of Intact vpu and nef genes in nonpathogenic SHIV is essential for acquisition of pathogenicity of this virus by serial passage in macaques

Use of the macaque model of human immunodeficiency virus (HIV) pathogenesis has shown that the accessory genes nef and vpu are important in the pathogenicity of simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV). We examined the ability of two nonpathogenic SHIVs, SHIV(PPC) and DeltavpuDeltanefSHIV(PPC), to gain pathogenicity by rapid serial passage in macaques. In this study, each virus was passaged by blood intravenously four times at 4-week intervals in macaques. Animals were monitored for 40 weeks for levels of CD4 T cells and quantitative measures of virus infection. DeltavpuDeltanefSHIV(PPC) maintained a limited phase of productive replication in the four animals, with no loss of CD4(+) T cells, whereas SHIV(PPC) became more pathogenic in later passages, judging by plasma viral load and viral mRNA in lymph nodes, infectious peripheral blood mononuclear cells and CD4(+) T cell loss. The nef, LTR, and env of the SHIV(PPC) viruses underwent numerous mutations, compared to DeltavpuDeltanefSHIV(PPC). This study confirms the seminal role that nef, LTR, and vpu could play in regulation of pathogenesis of HIV infection.     

Increased susceptibility to HIV-1 of peripheral blood lymphocytes in acute infection with Epstein-Barr virus

Epstein-Barr virus (EBV) is an important pathogen in human immunodeficiency virus (HIV)-infected individuals that causes lymphoma and other lymphoproliferative disorders upon disease progression; however, interaction between the two viruses during acute infection is not well known. Expression of CCR5, a major coreceptor for HIV, was enhanced on CD4+ T cells from patients with acute EBV infection. Furthermore, susceptibility of those cells to R5-HIV-1, but not X4-HIV-1, was increased. EBV effects on CCR5 expression on or susceptibility to R5-HIV-1 of CD4+ T cells did not require coinfection of the same cell with the two viruses, because CD4+ T cells from patients with acute EBV infection were not infected with EBV. Considering that both HIV and EBV are transmitted by intimate contact, such possible interaction between the two viruses may have implications for viral transmission and the pathogenesis of HIV disease.     

Virus and target cell evolution in human immunodeficiency virus type 1 infection

Human immunodeficiency virus (HIV) infection lead to a prolonged struggle between a rapidly evolving viral population and a potent immune response. In the vast majority of infected individuals, the virus wins this struggle. In my laboratory, we focus on understanding both the viral and immune factors that contribute to this outcome. The results of our studies and those of many others indicate that HIV can escape a potent immune response by a combination of mechanisms including rapid mutation, shedding of decoy antigens, modulation of host major histocompatibility complex, and destruction of cytotoxic T lymphocytes. The target cells for viral infection change as the virus evolves to use different chemokine coreceptors for entry. The initial targets are activated and resting memory T cells that express both CD4 and CCR5, but both naive and memory CD4 T cells are targeted by viruses capable of using CXCR4 for entry, and macrophages become the primary target cells when most CD4T cells are depleted. Compelling evidence isemerging that the availability of target cells for infection is as limiting for the spread of virus as the immune response.     

High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage

The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to illuminate the pathogenesis of HIV-associated disease. Here, we studied depletion and HIV infection frequencies of CD4 T cells from the gastrointestinal tract, bronchoalveolar lavage (BAL), and blood with the frequencies and functional profiles of HIV-specific T cells in these anatomically distinct sites in HIV-infected individuals. The major findings to emerge were as follows: (i) depletion of gastrointestinal CD4 T cells is associated with high frequencies of infected CD4 T cells; (ii) HIV-specific T cells are present at low frequencies in the gastrointestinal tract compared to blood; (iii) BAL CD4 T cells are not massively depleted during the chronic phase; (iv) infection frequencies of BAL CD4 T cells are similar to those in blood; (v) significantly higher frequencies and increased functionality of HIV-specific T cells were observed in BAL compared to blood. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells.     

The mucosal immune system: primary target for HIV infection and AIDS.

Despite intensive research, several questions remain regarding the pathogenesis of infection with HIV-1. Recently, it has been shown that simian immunodeficiency virus (SIV) selectively targets and destroys specific subsets of CD4+ T cells that are abundant in mucosal tissues but rare in peripheral lymphoid tissues. This finding could be highly relevant in explaining a major paradox in the infection and elimination of CD4+ T cells during HIV infection: the progressive decline in the number of CD4+ T cells in the blood, despite the paucity of HIV-infected cells in this tissue. This article discusses the hypothesis that infection with HIV and SIV, and the resulting disease, is governed by the state of cellular activation and the expression of chemokine receptors by specific subsets of CD4+ T cells residing in mucosal lymphoid tissues, rather than those found in the peripheral blood or lymph nodes.     

Intestinal double-positive CD4+CD8+ T cells are highly activated memory cells with an increased capacity to produce cytokines

Peripheral blood and intestinal CD4+CD8+ double-positive (DP) T cells have been described in several species including humans, but their function and immunophenotypic characteristics are still not clearly understood. Here we demonstrate that DP T cells are abundant in the intestinal lamina propria of normal rhesus macaques (Macaca mulatta). Moreover, DP T cells have a memory phenotype and are capable of producing different and/or higher levels of cytokines and chemokines in response to mitogen stimulation compared to CD4+ single-positive T cells. Intestinal DP T cells are also highly activated and have higher expression of CCR5, which makes them preferred targets for simian immunodeficiency virus/HIV infection. Increased levels of CD69, CD25 and HLA-DR, and lower CD62L expression were found on intestinal DP T cells populations compared to CD4+ single-positive T cells. Collectively, these findings demonstrate that intestinal and peripheral blood DP T cells are effector cells and may be important in regulating immune responses, which distinguishes them from the immature DP cells found in the thymus. Finally, these intestinal DP T cells may be important target cells for HIV infection and replication due to their activation, memory phenotype and high expression of CCR5.     

The Lymph Node in HIV Pathogenesis

Lymph nodes play a central role in the development of adaptive immunity against pathogens and particularly the generation of antigen-specific B cell responses in specialized areas called germinal centers (GCs). Lymph node (LN) pathology was recognized as an important consequence of human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. Investigation into the structural and functional alterations induced by HIV and Simian immunodeficiency virus (SIV) has further cemented the central role that lymphoid tissue plays in HIV/SIV pathogenesis. The coexistence of constant local inflammation, altered tissue architecture, and relative exclusion of virus-specific CD8 T cells from the GCs creates a unique environment for the virus evolution and establishment of viral reservoir in specific GC cells, namely T follicular helper CD4 T cells (Tfh). A better understanding of the biology of immune cells in HIV-infected lymph nodes is a prerequisite to attaining the ultimate goal of complete viral eradication.     

Antibody-dependent cellular cytotoxicity (ADCC)-mediated destruction of human immunodeficiency virus (HIV)-coated CD4+ T lymphocytes by acquired immunodeficiency syndrome (AIDS) effector cells

The acquired immunodeficiency syndrome (AIDS) is defined in clinical terms by the development of Kaposi's sarcoma and/or severe opportunistic infections in persons without predisposing conditions. A hallmark of the syndrome has been a decrease in the number of CD4⁺ T helper cells. The reduction in the frequency of the CD4⁺ lymphocytes has been postulated to be primarily the result of human immunodeficiency virus (HIV) tropism and cytophathogenicity for the T-cell subset. Yet only a small percentage of cells is actually infected with HIV. Recently, we provided evidence indicating that AIDS patients' natural killer cells can mediate normal levels of antibody-dependent cellular cytotoxicity (ADCC) despite exhibiting a defect in natural killer (NK) effector function (J Immunol 139:55, 1987). This finding prompted us to investigate whether AIDS patients' effector cells could mediate ADCC against circulating CD4⁺ T cells infected with or expressing HIV antigen. The findings reported herein demonstrate that AIDS effector cells can mediate lysis of CEM (CD4⁺ T-cell line) coated with HIV protein in the presence of HIV-specific antibody. Lysis was specific, as non-HIV-coated CEM or the addition of HIV-negative serum resulted in no lysis. We then examined HIV-coated peripheral blood-derived CD4⁺ T lymphocytes as targets in ADCC. We demonstrate that in the presence of HIV-specific antibody, HIV-coated CD4⁺ T lymphocytes serve as targets for ADCC by AIDS effector cells. The lytic activity obtained with AIDS effector cells was comparable to that obtained with normal effector cells. These results demonstrate that AIDS effector cells can mediate ADCC against HIV-coated CD4⁺ T lymphocytes and suggest that ADCC may play a rolein vivo in the pathogenesis of AIDS.