HLA-B宽特异性抗原表位Bw4对HCV特异性T细胞反应影响分析

目的 探讨HLA-B分子宽特异性抗原表位Bw4对丙型肝炎病毒(HCV)特异性T细胞反应的影响.方法 以有偿献血途径感染HCV患者86例为研究对象,采用聚合酶链反应-序列特异性引物(PCR-SSP)方法,进行HLA分型.采用ELISPOT技术观察HCV非结构蛋白NS3、NS4及NS5诱导T细胞分泌IFN-γ反应.结果 86例HCV感染者中Bw4/4纯合子患者29例(33.7％)、Bw4/6杂合子患者38例(44.2％)、Bw6/6纯合子患者19例(22.1％).Bw4/4纯合子、Bw4/6杂合子、Bw6/6纯合子HCV病毒载量分别为(3.98±0.32) Log(IU/ml)、(5.22±0.29) Log(IU/ml)、(5.04±0.38) Log(IU/ml),3组比较,HCV病毒载量差异具有统计学意义(P=0.0153).24例患者进行HCV非结构蛋白(NS3、NS4、NS5)诱导T细胞分泌IFN-γ反应,Bw4/4纯合子组HCV特异性T细胞反应率为50％ (5/10),反应强度中位数为70 SFU/106 PBMC(0～2020 SFU/106 PBMC),非Bw4/4纯合子组中,HCV特异性T细胞反应率为14.28％ (2/14),反应强度中位数为0 SFU/106 PBMC (0～200SFU/106 PBMC).两组比较,Bw4/4纯合子组反应强度明显高于非Bw4/4纯合子组,差异有统计学意义(P=0.0450),前者HCV特异性T细胞反应频率高于后者,差异接近有统计学意义(P=0.069).在Bw4/4纯合子组,HCV以NS5诱导的T细胞反应为主体,其反应频率为50％ (5/10),非Bw4/4纯合子组,NS5反应频率仅为7.14％(2/14),两者比较差异接近具有统计学意义(P=0.050).结论 携带Bw4/4纯合子HCV感染者,病毒载量较低,HCV特异性T细胞反应较强.Bw4可能通过增强HCV特异性T细胞免疫,进而产生对抗HCV复制的作用.     

中国HIV-1B''/C亚型感染者对自身病毒中和作用与疾病进展关系的研究

目的：探讨中国HIV-1 B’/C亚型感染者对自身病毒中和作用与疾病进展的关系。方法：将24例HIV-1 B’/C感染者自身原代病毒与同期和6个月自身血浆作用后,感染正常PBMC,培养7天测定p24抗原浓度,以正常人血浆加病毒悬液为对照。以抑制50%对照孔p24浓度的血浆最高稀释倍数的倒数计算中和抗体滴度,中和抗体滴度≥8倍为具有中和作用。结果：在同期血浆中和自身病毒试验中,3例缓慢进展者（SP）均具有中和作用,HIV组仅4例（4/21）具有中和作用,SP组中和抗体滴度明显高于HIV组。在6个月血浆中和自身病毒试验中,SP组中和抗体滴度明显增加,HIV组12例具有中和作用,SP组中和抗体滴度明显高于HIV组。中和抗体滴度与病毒载量呈明显的负相关。结论：疾病缓慢进展的HIV-1 B’/C亚型感染者对自身病毒中和作用明显高于HIV组,提示中和抗体在延缓疾病进程中发挥重要作用。     

中国人群HLA-B等位基因与HIV-1感染者疾病进程相关性研究

目的：通过对中国人群HIV-1感染典型进展者（Typical progressors，TP）和长期不进展者（Long-term nonpmgressors，LTNP）HLA-B等位基因的分布频率的研究，探讨中国人群HLA-B等位基因与HIV-1感染者疾病进程的关系。方法：采用整群随机抽样方法从河南、吉林、辽宁、新疆、云南五省收集356例未经抗病毒治疗的HIV-1感染者血样，其中289例典型进展者和67例长期不进展者。应用聚合酶链反应-序列特异性引物技术（PCR-SSP）对其HLA-B等位基因特异性进行检测，并分析了他们的等位基因纯合子情况及Bw4／Bw6血清型，比较二组差异。结果：发现4个HLA-B等位基因位点在中国HIV-1感染人群中的表达频率较高，分别是HLA-B^＊13（TP：11．8％；LTNP：15．7％）、HLA-B^＊15（TP：17．3％；LTNP：8．2％）、HLA-B^＊40（TP：12．5％；LTNP：17．9％）、HIA-B^＊51（TP：9％；LTNP：10．4％）。其中长期不进展组HLA-B^＊67的等位基因频率为4．5％，典型进展组HLA-B^＊67的等位基因频率为1．2％，前者明显高于后者，具有显著性差异（P=0．022，OR=0．26，95％CI=0．08-0．89）。典型进展组的B^＊15的等位基因频率（17．3％）显著高于长期不进展组（8．2％）（P=0．009，OR=2．34，95％CI=1．18～4．76）。结论：HLA-B^＊67等位基因可能与延缓中国HIV-1感染者疾病进程相关，HLA-B^＊15等位基因可能与加速中国HIV-1感染者疾病进程相关。     

HIV疾病进展中体液因素的作用

针对在研究ＨＩＶ疾病进展中体液因素的作用所举行的第一次会议上出现的不同观点，Ｆｕｓｔ Ｇ和他的同事们对这些相互对立的观点进行了总结，并根据最近的有关研究对此进行了分析。     

HIV-1Nef蛋白变异对艾滋病疾病进展影响机制的研究

人类免疫缺陷病毒（HIV-1、HIV-2）和猴免疫缺陷病毒（SIV）的Nef基因与病毒致病性有关，在疾病进展到AIDS期的过程中发挥重要作用。Nef可通过提高病毒颗粒感染性、激活CD4淋巴细胞及防止受感染细胞凋亡等多种途径促进HIV复制；Nef表位缺失可形成HIV免疫逃逸株，影响机体针对HIV病毒的免疫反应。Nef基因对HIV感染后AIDS疾病进展的影响机制至今仍无定论，本文就近年来此方面的研究，作一简要回顾。     

HIV-1Nef蛋白变异对艾滋病疾病进展影响机制的研究

人类免疫缺陷病毒(HIV-1、HIV-2)和猴免疫缺陷病毒(SIV)的Nef基因与病毒致病性有关,在疾病进展到AIDS期的过程中发挥重要作用。Nef可通过提高病毒颗粒感染性、激活CD4淋巴细胞及防止受感染细胞凋亡等多种途径促进HIV复制[1];Nef表位缺失可形成HIV免疫逃逸株,影响机体针对HIV病毒的免疫反应。Nef基因对HIV感染后AIDS疾病进展的影响机制至今仍无定论,本文就近年来此方面的研究,作一简要回顾。     

中国HIV-1病毒分离株的生物学特性与疾病进展关系的研究

目的　从HIV AIDS患者应用微量全血法分离中国HIV 1毒株 ,研究HIV 1的生物学特性与HIV AIDS疾病进展相关性。方法　建立微量全血法 ,从HIV AIDS全血标本中分离 17株HIV 1病毒分离株 ;检测这 17株病毒分离株嗜性和复制动力。结果　从 2 6例HIV AIDS病例中分离出HIV 1病毒 ,分离率为 6 5 .4 % (17 2 6 ) ,其中 17例HIV 1感染者的病毒分离率为 5 2 .9% (9 17) ,均为巨噬细胞嗜性 (M嗜性 ,NSI) ;9例AIDS患者的HIV 1病毒分离率为 88.9% (8 9) ,其中 7株为T细胞嗜性 (T嗜性 ,SI) ,1株为巨噬细胞嗜性。通过检测P2 4抗原确定 17株HIV 1病毒分离株的复制动力。在分离到的 17株HIV 1中 ,SI型病毒分离株与AIDS组显著相关 (P <0 .0 5 ) ;AIDS期的病毒分离株的复制动力明显高于HIV感染期 (P <0 .0 5 )。结论　微量全血法可用于病毒分离。 17株分离株的HIV 1复制动力与CD4 + T淋巴细胞计数呈线性负相关 ,与病毒载量呈正相关。     

HIV-1准种的变化与疾病进展关系的研究

目的　研究HIV 1准种的变化对疾病进展的影响。方法　PCR方法扩增HIV 1V3～V5区片段 ,采用HMA(异源双链泳动分析 )的方法分析 4 8例HIV/AIDS准种的变化 ,并结合HIV/AIDSCD4 T淋巴细胞计数及病毒载量的结果分析HIV 1准种的变化对疾病进程的影响。结果　在不同的疾病状态下 ,体内病毒变异是不相同的 ,在体内CD4 T淋巴细胞计数较高 ,血浆病毒载量低的个体内 ,病毒毒株有很强的变异特征 ,体内具有很高的准种复杂度 ;而在CD4 细胞数很低 ,病毒载量较高的个体 ,病毒基因变异较少 ,病毒准种较为单一。结论　HIV 1准种的变化与疾病进展相关。     

中国HIV-1 B'/C亚型感染者对异体病毒中和作用与疾病进展关系研究

目的 探讨中国HIV-1 B'/C亚型感染者对异体病毒中和作用与疾病进展的关系.方法 根据CD4 T淋巴细胞数量和有尤临床症状将HIV-1 B'/C亚型感染者分为HIV慢性感染组和AIDS组.将HIV-1感染者血清稀释(1/10～1/320)后,与在基因结构特点上同源性很低的3株HIV-1作用,以检测其中和作用.同时以正常人血清加病毒悬液为对照孔,能够抑制对照孔50%病毒复制的血清为中和作用阳性.将某个HIV-1感染者血浆能够中和异体病毒的个数占3个异体病毒的百分率定义为HIV-1感染者中和异体病毒的宽度;将某个HIV-1感染者血浆中和3个异体病毒抗体滴度的几何平均滴度定义为HIV-1感染者中和异体病毒的强度.结果 HIV-1慢性感染组与AIDS组之间中和异体病毒的宽度和强度差异有统计学意义,HIV-1慢性感染组显著高于AIDS组.HIV-1慢性感染组中和异体病毒的宽度和强度与病毒载量呈正相关,而AIDS组巾和异体病毒的宽度和强度与病毒载量没有显著的相关性.HIV-1慢性感染组和AIDS组中和异体病毒的宽度和强度与CD4 T淋巴细胞数均没有显著的相关性.结论 中国HIV-1B'/C亚型感染者不同疾病进展阶段针对异体病毒中和作用能力不同,HIV慢性感染组显著高于AIDS组,当疾病进展到AIDS期时,失去对异体病毒的中和作用,提示针对异体病毒的中和抗体与疾病进程有关.     

A murine monoclonal antibody specific for a novel broad antigen associated with HLA-Bw4

Serological analysis of the reactivity of a murine monoclonal antibody, HA113, towards lymphocytes from a random panel of 85 cell donors, and members of four families, indicated that HA113 recognizes a public specificity, which is different from the classical Bw4 antigen as defined by human alloantisera.     

Impact of tuberculosis on HIV-1 replication,diversity, and disease progression

HIV and Mycobacterium tuberculosis not only co-circulate throughout the developing world but each has contributed to prevalence and mortality caused by the other. Several reports have described how HIV-1 increases the incidence of new M. tuberculosis infections, exacerbates the severity of tuberculosis (TB), and re-activates latent M. tuberculosis. However, the converse relationship is more difficult to understand considering TB can emerge in asymptomatic individuals and as an opportunistic infection during AIDS. Development of TB in HIV infected individuals with higher CD4 cell counts (> 200/mm3) appears to increase the rate of disease progression and mortality. Higher viral loads, increased HIV-1 diversity, and changes in cytokine/chemokine levels in HIV-infected individuals with TB appear to be related to a localized immune stimulation. Specifically, increased levels of TNF alpha and MCP-1, induced by TB, may activate HIV replication in lymphocytes, monocytes, and macrophages that are resident or have migrated to M. tuberculosis infected organs (e.g. pleura or lung). The HIV-1 found in blood following this TB-mediated burst in load and diversity appear to be phylogenetically-related to HIV-1 clones that have evolved independently in the lung or pleural compartments, now infected by M. tuberculosis.     

No association of KIR genes with Behcet's disease

Behcet's disease (BD) is thought to be caused by multiple genetic, environmental and immunological factors, one of the most prominent being the strong association with human leucocyte antigen (HLA)-Bw51, an HLA-Bw4-associated allele. We examined the presence/absence of 14 killer cell immunoglobulin-like receptors (KIRs) and their ligands in 134 Turkish individuals with BD and compared the results with those of 154 ethnically matched controls. Although KIR3DL1 with its ligand (HLA-Bw4) was significantly increased in the patients with BD (P = 0.0003), this no longer applied when the patients and controls were categorised by HLA-Bw51 status. Thus, no association was identified between presence or absence of any of the 14 KIR genes studied and BD. In addition, we did not find any associations of KIR with various manifestations of the disease nor with gender or age of onset.     

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.     

Supertypic HLA-Bw4 antigen detected by a new monoclonal antibody

A monoclonal antibody, HLAO1, was prepared by immunizing BALB/c mice with human lymphocytes of known HLA genotype. The monoclonal antibody is cytotoxic, of the IgG 2b isotype and binds to a protein of Mr 43,000 noncovalently associated with the beta 2-microglobulin. Genetic analysis proved complete concordance in the expression of the antigenic determinant defined by this monoclonal antibody and the presence of a supertypic (public) antigen, the HLA-Bw4. As expected, the monoclonal antibody also reacted with the antigens of HLA-A locus, A23, A24, and A32. The computer analysis of HLAO1 antibody binding to the Bw4/Bw6 heterozygous lymphocytes gave the approximate number of antigenic determinants, n = 2.2 X 10(4)/cell, and Ka = (5.9 +/- 0.8) X 10(9) M-1. Besides its potential immunochemical applications, the HLAO1 monoclonal antibody can become a useful tool in routine cytotoxicity typing of HLA antigens on peripheral lymphocytes.     

HIV-1 IgA specific serum antibodies and disease progression during HIV-1 infection

OBJECTIVE: To evaluate the role of serum human immunodeficiency virus type 1 immunoglobulin A (HIV-1 IgA) antibodies in the progression of HIV-1 infection in relation to viral load and CD4 cell counts. METHODS: Sequential serum specimens were obtained from 218 homosexual men: 123 HIV-1 seropositives, 24 HIV-1 seroconverters, and 71 HIV-1 seronegatives. HIV-1 IgA antibodies were tested blindly by enzyme-linked immunosorbent assay and Western blot. T-lymphocyte subsets were measured by flow cytometry. Viral plasma load was determined by a sensitive branched DNA assay. RESULTS: HIV-1 IgA antibodies with a titer greater than or equal to 50 were detected among 50% of the seroconverters, 27% of the HIV-1-seropositive asymptomatic subjects, 25% of lymphadenopathy, and 23% of HIV-1-related symptomatic subjects. Among patients with the acquired immune deficiency syndrome, the prevalence of virus-specific IgA antibodies (55%) was significantly higher (p < 0.03) as compared with the HIV-1-seropositive asymptomatic subjects, lymphadenopathy and HIV-1-related symptomatic patients, but not versus the seroconverters (p = 0.8). IgA antibodies to HIV-1 gP160 were the most prevalent among all subjects tested. A significant decrease in CD4 cell counts was observed after HIV-1 seroconversion. Viral load was slightly higher among the seroconverters who demonstrated higher (> or =50) HIV-1 IgA levels. CONCLUSIONS: HIV-1 IgA serum antibodies did not predict the progression of the disease. Correlation between HIV-1 IgA antibodies titer, viral load, and CD4 cell counts was not detected.     

Dynamics of naive and memory CD4+ T lymphocytes in HIV-1 disease progression

Understanding the dynamics of naive and memory CD4+ T cells in the immune response to HIV-1 infection can help elucidate typical disease progression patterns observed in HIV-1 patients. Although infection markers such as CD4+ T-cell count and viral load are monitored in patient blood, the lymphatic tissues (LT) have been shown to be an important viral reservoir. Here, we introduce the first comprehensive theoretical model of disease progression based on T-cell subsets and virus circulating between the two compartments of LT and blood. We use this model to predict several trademarks observed in adult HIV-1 disease progression such as the establishment of a setpoint in the asymptomatic stage. Our model predicts that both host and viral elements play a role in determining different disease progression patterns. Viral factors include viral infectivity and production rates, whereas host factors include elements of specific immunity. We also predict the effect of highly active antiretroviral therapy and treatment cessation on cellular and viral dynamics in both blood and LT.