CD8^＋T淋巴细胞非细胞毒性抗HIV作用研究进展

细胞免疫在抗病毒感染中发挥着至关重要的作用。人类免疫缺陷病毒(HIV)感染所引起的细胞免疫反应是由CD8^ T淋巴细胞的亚群细胞毒性T细胞(CTL)介导的先天免疫。CIIs一方面通过细胞毒性作用杀伤感染的细胞，另一方面分泌可溶性抗病毒因子(CAF)发挥直接的抗病毒作用，因此成为HIV感染中细胞免疫的重要组成部分。本就HIV感染这一疾病过程中CD8^ T淋巴细胞所发挥的非细胞毒性抗病毒效应作一概述。     

HIV-1感染疾病缓慢进展者CD8+T淋巴细胞非细胞毒性免疫应答作用的研究

目的 探讨HIV-1感染疾病缓慢进展者CD8+T淋巴细胞非细胞毒性抗病毒应答功能(CNAR)的变化.方法 应用密度梯度离心法、免疫磁珠法纯化健康人CD4+T淋巴细胞和HIV感染者CD8+T淋巴细胞,用HIV毒株SF-33感染健康人CD4+T淋巴细胞,并加入不同疾病进程HIV感染者CD8+T淋巴细胞共培养,收集培养上清,应用ELISA方法测定上清中HIV-1 p24含量.结果 我们研究发现缓慢进展组(slow progressors,SP)、HIV典型进展组(typical progressors,TP)、健康对照组及AIDS组中CNAR功能依次下降(89%>77%>73%>61%),各组间的下降差异均有统计学意义(P<0.05);在HIV感染者中,CNAR功能与CD4+T细胞绝对计数呈显著正相关;与病毒载量无显著相关性.结论 CNAR功能对HIV感染疾病不进展可能具有保护作用.     

HIV血清阳性个体中HIV特异性的细胞毒性T淋巴细胞

病毒特异性的细胞毒性T淋巴细胞(CTL)对病毒感染细胞的杀伤作用是宿主抗病毒感染的一种主要机制。本文报导在人免疫缺陷病毒(HIV)感染的个体体内存在有HIV特异性的细胞毒性T淋巴细胞。作者首先建立了实验组和对照组的B淋巴细胞系,其中实验组B细胞来自8例HIV血清阳性的男性同性恋患者,而对照组B细胞来自5例HIV血清阴性个体。然后用HIV-牛痘重组病毒载体感染这些B细胞株,并将其作为靶细胞用于细胞毒活性的测     

HIV/AIDS患者CD28在外周血CD4+、CD8+ T细胞上的表达变化

目的　研究国内HIV AIDS患者CD2 8在外周血CD4 + 、CD8+ T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 36例AIDS患者的外周血CD4 + 、CD8+ T淋巴细胞表面的CD2 8分子的表达 ,用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　CD4 + CD2 8+ T细胞的绝对计数与百分比、CD8+ CD2 8+T细胞的百分比均显示为正常对照组 >HIV感染组 >AIDS组 ;而CD8+ CD2 8+ T细胞的绝对计数显示HIV感染组和对照组显著大于AIDS组 ,HIV感染组与对照组间差异无显著性。CD4 + 、CD2 8+ CD4 + T淋巴细胞计数与血浆病毒载量显著负相关。结论　HIV AIDS患者外周血CD2 8在CD4 + 、CD8+ T淋巴细胞上表达随着病情进展而降低 ,反映了细胞免疫功能随着疾病进展损害逐渐加重 ,是判断病情进展的指标。     

丙型肝炎病毒T细胞抗原表位及其免疫学意义

HCV引起免疫损伤的机制至今尚不清楚。细胞免疫可能起了重要作用 ,尤其是细胞毒性T淋巴细胞 (CTL Tc)的作用。进行丙型肝炎病毒T细胞表位的研究有助于阐明HCV持续性感染机制 ,并为研制抗病毒疫苗奠定基础。本文对近年来HCVT细胞抗原表位的研究进展作一综述     

中国HIV感染者细胞毒性淋巴细胞与CD4~+CD25~+调节性T细胞相关性研究

目的：对中国HIV感染者NK细胞、CD8^＋T细胞及胞内穿孔素、颗粒酶-B表达与CD4^＋CD25^＋Foxp3^＋调节性T细胞水平的相关性进行研究,探讨调节性T细胞在HIV感染中的作用机制。方法：选取73名HIV/AIDS患者（长期不进展组、无症状HIV组、AIDS组）,应用流式细胞仪胞内染色技术检测NK细胞、CD8^＋T细胞数量及胞内穿孔素、颗粒酶-B表达水平,分析其与CD4^＋CD25^＋Foxp3^＋调节性T细胞水平的相关性。结果：CD4^＋CD25^＋Foxp3^＋调节性T细胞百分率与NK细胞、CD8^＋T淋巴细胞数量呈明显负相关（P〈0.01）,与CD8^＋T细胞内穿孔素、颗粒酶-B表达百分率呈明显正相关（P〈0.05）,与NK细胞内穿孔素、颗粒酶-B表达水平绝对值负相关（P〈0.01）,与CD8＋T细胞内颗粒酶-B表达绝对值呈明显负相关（P〈0.01）,与CD8^＋T细胞内穿孔素表达绝对值无明显相关性（P〉0.05）。CD4^＋CD25^＋Foxp3^＋调节性T细胞绝对值与CD8^＋T细胞内穿孔素、颗粒酶-B表达百分率呈明显负相关（P〈0.05）。结论：中国HIV感染者细胞毒性淋巴细胞数量功能的变化与调节性T细胞显著相关,提示高水平的调节性T细胞可能与细胞毒性淋巴细胞耗竭相关,可能为导致疾病进展的原因之一。     

无症状期HIV感染者CD4+和CD8+T细胞计数与病毒载量的关系

艾滋病是由人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染所导致的以免疫系统功能缺陷为特征的慢性高致死率传染病.CD4+T细胞是HIV损害的主要靶细胞,HIV可引起CD4+T淋巴细胞进行性丢失与功能受限[1-2].在HIV感染早期,CD8+T细胞增多并通过分泌各种细胞因子杀死被病毒感染的靶细胞,其高表达与病毒量载量呈正相关[3],而随着疾病进展,CD8+T细胞会消耗性减少.CD4+T细胞、CD8+T细胞计数与病毒载量的相关性一直为研究者关注[4-6].本研究检测了无症状期感染者,外周血CD4+T细胞和CD8+T细胞计数与病毒载量并分析它们的相关性.     

中国HIV感染长期不进展者CD4+CD25+Foxp3+调节性T细胞变化研究

目的 对中国HIV感染长期不进展者(LTNP)CD4+CD25+Foxp3+调节性T细胞水平及其与疾病进展相关性进行研究,探讨CD4+CD25+Foxp3+ 调节性T细胞在LTNP保护机制中发挥的作用.方法 选取74名HIV-1感染者(LTNP、典型进展HIV组、AIDS组)及16名健康对照,应用流式细胞仪胞内染色技术在单细胞水平检测CD4+CD25+Foxp3+调节性T细胞表达水平,分析其与CD4+ T细胞数量、病毒载量、淋巴细胞活化、凋亡水平的相关性.结果 中国HIV感染LTNP CD4+CD25+Foxp3+ T细胞百分率明显低于典型进展HIV、AIDS组及健康对照组(P<0.05).HIV/AIDS患者CD4+CD25+Foxp3+ T细胞百分率与CD4+ T细胞显著负相关(r=-0.509,P<0.001),与病毒载量明显正相关(r=0.414,P<0.01),与CD4、CD8+ T细胞表面CD38、CD95表达水平明显正相关(P<0.05),与CD4、CD8+ T细胞表面HLA-DR表达无显著相关性.结论 中国HIV感染LTNP CD4+CD25+Foxp3+ 调节性T细胞百分率明显低于典型进展者,提示调节性T细胞与LTNP保护机制相关.     

中国HIV/AIDS患者T细胞及调节性T细胞CTLA-4表达与疾病进展关系研究

目的 对中国HIV感染者T细胞及凋节性T细胞CTLA-4表达与HIV疾病进展的相关性进行研究,探讨CTLA-4在HIV感染中的作用.方法 选取58名HIV/AIDS患者(长期不进展组、无症状HIV组、AIDS组),应用流式细胞仪胞内染色技术检测T细胞及CD4+CD25+Foxp3+调节性T细胞内CTLA-4表达水平,分析其与CD4+T细胞、病毒载量、淋巴细胞活化凋亡水平的相关性.结果 长期不进展组、无症状HIV组、AIDS组CD4+T细胞内CTLA-4表达水平依次增岛(P<0.05);与CD+T细胞显著负相关(P<0.01),与CD8+T细胞活化(CD38表达)、凋亡水平(CD95表达)及CD4+T细胞凋亡水平显著相关(P<0.05),与病毒载量无显著相关性.长期不进展组、无症状HIV组、AIDS组CD8+T细胞内CTLA-4表达水平差异无统计学意义;与CD4+T细胞、病毒载量、CD4,'+>、CD8+T细胞活化及凋亡水平均无显著相关性.CD4+CD25+Foxp3+T细胞内CTLA-4表达水平长期不进展组明显低于无症状HIV组及AIDS纽(P<0.05);与CD4+T细胞显著负相关(P<0.05);与CD4+、CD8+T淋巴细胞活化(HLA-DR表达)显著相关(P<0.01).结论 中国HIV感染者CD4+T细胞及CD4+CD25+Foxp3+调节性T细胞内CTLA-4表达水平与疾病进展及免疫活化状态显著相关,参与HIV感染免疫平衡的调节.     

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。     

Will we be able to 'spot' an effective HIV-1 vaccine?

Many HIV-1 vaccine efforts have heavily emphasized class I-restricted CD8(+) cytotoxic T lymphocytes (CTLs) as a potentially important arm of immunity. Commonly used CTL assays describe only specificity and frequency, and not antiviral effects. However, increasing evidence indicates that CTL antiviral function is determined by the complex interplay of multiple virologic and cellular factors, and thus these measurements are an incomplete reflection of CTL efficacy. Our current understanding of the factors determining HIV-1-specific CTL antiviral efficacy is inadequate to interpret fully the significance of detected CTLs in vaccine and pathogenesis studies. To assess CTLs as a protective immune response, it will be crucial to elucidate these mechanisms and/or devise new assays that directly reflect the interaction of CTLs and HIV-1.     

Triggering of TLR‐3, ‐4, NOD2, and DC‐SIGN reduces viral replication and increases T‐cell activation capacity of HIV‐infected human dendritic cells

A variety of signals influence the capacity of dendritic cells (DCs) to mount potent antiviral cytotoxic T‐cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors, such as TLR and C‐type lectines, influences DC biology and affects their susceptibility to HIV infection. Yet, whether the combined effects of PPRs triggering and HIV infection influence HIV‐specific (HS) CTL responses remain enigmatic. Here, we dissect the impact of innate immune sensing by pathogen recognition receptors on DC maturation, HIV infection, and on the quality of HS CTL activation. Remarkably, ligand‐driven triggering of TLR‐3, ‐4, NOD2, and DC‐SIGN, despite reducing viral replication, markedly increased the capacity of infected DCs to stimulate HS CTLs. This was exemplified by the diversity and the quantity of cytokines produced by HS CTLs primed by these DCs. Infecting DCs with viruses harboring members of the APOBEC family of antiviral factors enhanced the antigen‐presenting skills of infected DCs. Our results highlight the tight interplay between innate and adaptive immunity and may help develop innovative immunotherapies against viral infections.     

Immunogenetics of HIV disease

Host genetic factors are a major contributing factor to the inter-individual variation observed in response to human immunodeficiency virus (HIV) infection and are linked to resistance to HIV infection among exposed individuals, as well as rate of disease progression and the likelihood of viral transmission. Of the genetic variants that have been shown to affect the natural history of HIV infection, the human leukocyte antigen (HLA) class I genes exhibit the strongest and most consistent association, underscoring a central role for CD8⁺ T cells in resistance to the virus. HLA proteins play important roles in T-cell-mediated adaptive immunity by presenting immunodominant HIV epitopes to cytotoxic T lymphocytes (CTLs) and CD4⁺ T cells. Genetic and functional data also indicate a function for HLA in natural killer cell-mediated innate immunity against HIV by interacting with killer cell immunoglobulin-like receptors (KIR). We review the HLA and KIR associations with HIV disease and discuss the mechanisms underlying these associations.     

Of mice and men: cytotoxic T cells and AIDS pathogenesis

CD8+ cytotoxic T lymphocytes (CTLs) represent a first line of defense against HIV infection, although their precise role in disease pathogenesis remains enigmatic. They play an important part in viral control but may also contribute to disease progression through destruction of CD4+ helper T cells. The role of CTLs in lymphocytic choriomeningitis virus (LCMV) infection in mice has been studied extensively, and the effects of CTL activity on host and virus are well defined. Although LCMV is not a retrovirus, it shares salient features with HIV, including a wide tropism, a capacity to persist, and genetic instability. The diseases caused by LCMV and HIV are linked by common immune effector mechanisms and, potentially, immunopathologies. Understanding the well-characterized immune responses in LCMV infection may therefore cast light on the role of CTLs in HIV disease.     

巨细胞病毒抗原PP65495-503特异性细胞毒性T细胞受体互补决定区3研究概况

巨细胞病毒(CMV)侵入机体后能引起T细胞特异性活化、增殖、应答,其中CD8+的细胞毒性T细胞(CTLs)主要由T细胞受体互补决定区3(TCR CDR3)识别HLA-肽复合物.通过对CMV感染者的TCR CDR3区序列及频率进行检测和分析.可深入了解机体应答状况,并能为CMV感染的诊断和治疗提供新思路.对HLA-A2-...     

The induction of murine cytotoxic T lymphocytes by bluetongue virus

Summary After inoculation with live bluetongue virus, mice produced cytotoxic T lymphocytes (CTL) which showed virus and H-2 restriction. Inactivated preparations failed to induce CTLs. On secondaryin vitro stimulation, specifically sensitised memory cells also produced high numbers of CTLs. The need for replicating virus to induce primary CTLs, evidence for partial type specificity and the role which cell-mediated immunity might play in the early stages of a bluetongue virus infection are discussed.With 1 Figure     

Cytotoxic T lymphocyte responses to human immunodeficiency virus: control and escape

Effective preventive and therapeutic intervention in individuals exposed to or infected with human immunodeficiency virus (HIV) depends, in part, on a clear understanding of the interactions between the virus and those elements of the host immune response which control viral replication. Recent advances have provided compelling evidence that cytotoxic T lymphocytes (CTLs) constitute an essential component of protective antiretroviral immunity. Here, we review briefly the significance of this work in the context of previous studies, and outline the mechanisms through which HIV evades CTL activity.     

ANTI-HIV AND -SIV IMMUNITY IN THE VAGINA

Most HIV infections worldwide are transmitted through heterosexual contact. In order to develop vaccination strategies, the basic biology of the immune system in female reproductive tract and the full range of vaginal immune responses that occur during natural HIV infection must be understood. The cervicovaginal mucosa contains a complete set of immune cells, including antigen-presenting cells, CD4+ and CD8+ T cells, and B cells. The CVS of HIV-infected women and SIV-infected female rhesus macaques contain variable levels of antiviral antibodies. Some of this variation is due to the effects of female ovarian hormone cycle. IgG antibodies make up the bulk of the antiviral antibody response. However, IgA antibodies are present at lower levels. HIV/SIV-specific CD8+ cytotoxic T lymphocytes are present in the cervicovaginal mucosa of infected women and rhesus macaques. A vaccine that can elicit strong antiviral immunity may provide protection for hetorosexual HIV-1 transmission.     

特异性细胞毒性T细胞检测方法的建立及其在重组痘苗病毒活疫苗细胞免疫研究中的应用

报道了用ＣＢＡ／Ｊ小鼠、Ｌ９２９细胞及ＭＴＴ比色法建立的特异性细胞毒性Ｔ细胞（ＣＴＬ）的检测方法及其在重组痘苗病毒活疫苗细胞免疫研究中的应用。通过检测痘菌病毒特异性初发ＣＴＬ的动态变化及其二次反应ＣＴＬ，表明，本法能较好地检测初发及二次反应ＣＴＬ水平的变化。用本法检测了不同启动子控制下的表达Ｅｐｓｔｅｉｎ－Ｂａｒｓ（ＥＢ）病毒膜抗原（ＥＢＶ－ＭＡ）的重组痘菌病毒ＥＢＶ－ＭＡ特异性ＣＴＬ、以及与表达人白细胞介素－２的重组痘苗病毒联合免疫时的ＥＢＶ－ＭＡ特异性ＣＴＬ。结果表明，Ｐ７５００启动子表达的ＥＢＶ－ＭＡ比Ｐ１１０００启动子表达的ＥＢＶ－ＭＡ诱导的ＥＢＶ－ＭＡ特异性ＣＴＬ高，但无显著性差异。当上述重组痘苗病毒与表达人白细胞介素－２的重组痘苗病毒联合免疫时，均能使二者的ＥＢＶ－ＭＡ特异性ＣＴＬ增高，但增高幅度本身及其二者之间均无显著性差异。     

Anti-HIV and -SIV immunity in the vagina

Most HIV infections worldwide are transmitted through heterosexual contact. In order to develop vaccination strategies, the basic biology of the immune system in female reproductive tract and the full range of vaginal immune responses that occur during natural HIV infection must be understood. The cervicovaginal mucosa contains a complete set of immune cells, including antigen-presenting cells, CD4+ and CD8+ T cells, and B cells. The CVS of HIV-infected women and SIV-infected female rhesus macaques contain variable levels of antiviral antibodies. Some of this variation is due to the effects of female ovarian hormone cycle. IgG antibodies make up the bulk of the antiviral antibody response. However, IgA antibodies are present at lower levels. HIV/SIV-specific CD8+ cytotoxic T lymphocytes are present in the cervicovaginal mucosa of infected women and rhesus macaques. A vaccine that can elicit strong antiviral immunity may provide protection for hetorosexual HIV-1 transmission.