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1.
本文简述近几年来丙型肝炎病毒(HCV)感染与宿主细胞免疫应答之间关系的研究进展,重点对HCV感染后体内CD4^+T细胞、CD8^+T细胞和细胞毒性T淋巴细胞(CTL)的免疫应答及其在免疫致病中的作用进行了讨论。 相似文献
2.
双歧杆菌活菌制剂对慢性乙肝病人细胞免疫功能影响的观察 总被引:2,自引:1,他引:2
在应用双歧杆菌活菌制剂治疗慢乙肝期间,重点观察了T细胞亚群(CD3,CD4,CD8)、NK细胞(CD(16))、白细胞介素Ⅱ(IL-2)分泌细胞、肿瘤坏死因子(TNF)等细胞免疫指标治疗前后的动态变化,同时观察了病人血内毒素水平的动态变化和乙肝病毒标志物(HBVM)的改变。结果表明:(1)与对照组比较,双歧杆菌活菌制剂可使慢乙肝病人CD3+,CD4+数目明显增多,而对CD8+细胞数目无明显影响;(2)双歧杆菌活菌制剂可使CAH组的CD16+细胞显著增多(p<0.05);使CAH组和CPH组的IL-2分泌细胞均有非常显著和显著增加(分别p<0.01和p<0.05);(3)CAH组病人血中内毒素和TNF水平在双歧杆菌活菌制剂治疗后,匀出现非常显著降低(p<0.01);CPH组TNF水平较对照组无显著变化,但内毒素水平较对照组显著降低(p<0.05);(4)满疗程后(60天)CAH组有6例,CPH组有5例HBeAg阴转(分别为26.06%和25.0%),而对照组仅2例阴转(13.33%),两治疗组与对照组比较有显著性差异(p<0.05)。 相似文献
3.
人类免疫缺陷病毒与程序性T细胞死亡 总被引:1,自引:0,他引:1
关于人类免疫缺陷病毒(HIV)感染引发AIDS的发病机制尚不明确,本文介绍了一种新的致病机制,认为HIV感染机体后可能诱导CD4^+和CD8^+T细胞发生程序性死亡,从而导致AIDS产生,并依此机制探讨有关抗HIV感染的新途径。 相似文献
4.
将编码丙型肝炎病毒(HCV)E2蛋白417~750位氨基酸的DNA片段 克隆到真核表达载体pcDNA 3.1(-)中的CMV IE启动子下游,构建成HCV E2重组真核表达质粒 pcE2。ELISA法检测pcE2 DNA免疫兔血清中的E2抗体变化和维持规律,结果显示免疫20d已有 抗体产生,30d后开始进入高峰,40d时达到最高值,至第90d抗体水平保持平稳,抗体滴度 达到1∶1600左右。流式细胞计数仪(FACS)检测pcE2 DNA免疫鼠CD4+、CD8+T淋巴细胞变 化情况,与注射空载体pCDNA3.1(-)的阴性鼠相比,CD4+淋巴细胞水平略有上升,CD8+ 细胞水平有较大升高,增幅达35.46%。免疫组化检测结果显示注射pcE2的小鼠组织中有明显 的阳性着色,而注射pcDNA3.1(-)的对照组小鼠免疫组化结果为阴性。以上结果表明:pcE2 在实验动物内表达出的HCV E2蛋白可以引起免疫动物的体液免疫应答和细胞免疫应答,尤其 是MHC-1限制性杀伤性CD8+T淋巴细胞水平的提高对清除 病毒是十分有利的,因此HCV E2 DNA免疫有可能成为预防和治疗HCV感染的一条新途径。 相似文献
5.
CD28共刺激可促HIV阳性患者CD+4T细胞增殖CD+4T细胞是人免疫缺陷病毒(HIV)感染的主要细胞。由于在体外难以诱导HIV感染者的自体CD+4T细胞增殖,因此限制了许多疗法如基因治疗、免疫重建疗法的应用。已知在T细胞活化中,T细胞受体(TCR... 相似文献
6.
将含有鸡传染性支气管炎病毒 S1 基因c D N A 的重组转移质粒p S X I V V I+ X3 S1 . Holte 和p S X I V V I+ X3/4 S1 . Holte 分别与粉纹夜蛾核型多角体病毒 Tn N P V S V I- G D N A( O C C- ,gal+ ) 共转染草地夜蛾( Sf9) 细胞,经空斑纯化得到重组病毒 Tn N P V( X3) S1 . Holte O C C+ 和 Tn N P V( X3/4) S1 . Holte O C C+ 。将重组毒株分别感染 Tn5 B1 细胞,并进行 S D S P A G E 与 Westernblot 检测。结果表明, Tn N P V( X3/4) S1 . Holte O C C+ 在感染的细胞中高效表达了 S1 蛋白, S D S P A G E 凝胶薄层色谱分析结果显示,感染病毒后72 h S1 蛋白的表达量占细胞内总蛋白量的35 .8 % ,而 Tn N P V( X3) S1 . Holte O C C+ 感染的细胞内检测不出 S1 蛋白。经分析认为这一差异主要来自 S1 基因翻译起始位点及其附近的周围环境。 相似文献
7.
目的和方法:将可产生含有HSVTK基因逆转录病毒的包装细胞与BEL7402肝癌细胞混合后,接种于裸鼠皮下,复制肝癌模型。确定HSVTK基因转移后,给予动物注射GCV,观察HSVTK/GCV系统基因治疗实验性肝癌的在体疗效。结果:在体条件下,逆转录病毒可将HSVTK基因部分转导至肝癌细胞;GCV作用后,TK+中瘤细胞的生长受到明显抑制;电镜观察发现,GCV杀伤TK+肿瘤细胞的作用主要体现在细胞核;虽然组化染色分析表明TK基因转移效率只有10%~30%,但测量肿瘤体积显示HSVTK/GCV系统杀伤肝癌细胞的效果依然明显,故其作用机制可与“旁观者效应”有关。结论:HSVTK/GCV“自杀”基因系统有可能成为基因治疗肝癌的有效方法 相似文献
8.
本实验以人卵巢癌细胞株(COC1)为模型,观察诱导分化剂二甲亚砜(DMSO)与维甲酸(RA)对该细胞生长增殖、DNA合成和转化生长因子β1(TGFβ1)在细胞内表达的影响。结果显示:DMSO与RA对人卵巢细胞COC1生长有明显的抑制作用,生长曲线表明作用5天后其生长抑制率分别为62.7%和42.1%;3H-胸腺嘧啶核苷(3H-TdR)掺入实验说明DMSO组与RA组的单位时间计数率(CPM)明显低于对照组(P<0.01)。用药3天后百分掺入抑制率分别为60.4%与37.9%,表明DMSO与RA抑制COC1细胞的DNA合成;免疫细胞化学反应表明,DMSO或RA处理5天后,对照组细胞TGFβ1表达为阳性,定位于胞浆,而处理组细胞TGFβ1呈阴性或弱阳性反应。以上结果提示DMSO和RA对人卵巢癌细胞有一定的诱导分化作用。 相似文献
9.
对362名无症状高滴度HBsAg携带者用RIA法检测HBeAg、Anti-HBe、Anti-HCV、Anti-HDV。结果表明,HBeAg阳性率随HBsAg滴度的增高而增加,且有显著性差异(P<0.05)。重叠感染以HBV+HCV最高,占27.6%;其次是HBV+HDV,占9.1%;HBV+HCV+HDV最少,占6.4%。但是,以上重叠感染率均与HBsAg滴度及/或HBeAg阳性率高低无关(P>0.05)。调查显示,无症状HBsAg携带者中HBV+HCV,或HBV+HDV,或HBV+HCV+HDV的重叠感染均可发生。 相似文献
10.
本研究结合光镜免疫组化和组织化学方法,在光镜和电镜下观察了人外周血树突状细胞(DC)对LAK细胞杀伤人肝癌H7402细胞的影响。结果显示,(1)DC不仅能与LAIC细胞形成花环,还能与LAK、H(7402)细胞相互接触形成细胞簇,常见呈明显坏死状态的H(7402)周围有DC和LAK细胞围绕;(2)与H(7402)+LAK细胞组相比,在H(7402)+LAK+DC组中,肿瘤细胞的坏死程度明显加重。提示人外周血DC在细胞免疫抗肿瘤过程中起重要作用。 相似文献
11.
Antibody-independent antiviral function of memory CD4+ T cells in vivo requires regulatory signals from CD8+ effector T cells 总被引:3,自引:0,他引:3
Previous studies have shown that vaccine-primed CD4(+) T cells can mediate accelerated clearance of respiratory virus infection. However, the relative contributions of Ab and CD8(+) T cells, and the mechanism of viral clearance, are poorly understood. Here we show that control of a Sendai virus infection by primed CD4(+) T cells is mediated through the production of IFN-gamma and does not depend on Ab. This effect is critically dependent on CD8(+) cells for the expansion of CD4(+) T cells in the lymph nodes and the recruitment of memory CD4(+) T cells to the lungs. Passive transfer of a CD8(+) T cell supernatant into CD8(+) T cell-depleted, hemagglutinin-neuraminidase (HN)(421-436)-immune muMT mice substantially restored the virus-specific memory CD4(+) response and enhanced viral control in the lung. Together, the data demonstrate for the first time that in vivo primed CD4(+) T cells have the capacity to control a respiratory virus infection in the lung by an Ab-independent mechanism, provided that CD8(+) T cell "help" in the form of soluble factor(s) is available during the virus infection. These studies highlight the importance of synergistic interactions between CD4(+) and CD8(+) T cell subsets in the generation of optimal antiviral immunity. 相似文献
12.
Ross B. Fulton Kayla A. Weiss Lecia L. Pewe John T. Harty Steven M. Varga 《Journal of virology》2013,87(23):12694-12700
Respiratory virus infections in the elderly result in increased rates of hospitalization and death. Respiratory syncytial virus (RSV) is a leading cause of severe virus-induced respiratory disease in individuals over the age of 65. CD8 T cells play a critical role in mediating RSV clearance. While it is clear that T cell immunity declines with age, it is not clear to what extent the CD8 T cell response to RSV is altered. Using aged BALB/c mice, we demonstrated that RSV-specific CD8 T cell responses were significantly reduced in the lungs of aged mice at the peak of the T cell response and that this decrease correlated with delayed viral clearance. Despite a decrease in the overall numbers of RSV-specific CD8 T cells during acute infection, their capacity to produce effector cytokines was not impaired. Following viral clearance, the RSV-specific memory CD8 T cells were similar in total number and phenotype in young and aged mice. Furthermore, following infection with a heterologous pathogen expressing an RSV epitope, RSV-specific memory CD8 T cells exhibited similar activation and ability to provide early control of the infection in young and aged mice. These data demonstrate a decrease in the capacity of aged mice to induce a high-magnitude acute CD8 T cell response, leading to prolonged viral replication, which may contribute to the increased disease severity of RSV infection observed for aged individuals. 相似文献
13.
Trapp S von Einem J Hofmann H Köstler J Wild J Wagner R Beer M Osterrieder N 《Journal of virology》2005,79(9):5445-5454
Key problems using viral vectors for vaccination and gene therapy are antivector immunity, low transduction efficiencies, acute toxicity, and limited capacity to package foreign genetic information. It could be demonstrated that animal and human cells were efficiently transduced with equine herpesvirus 1 (EHV-1) reconstituted from viral DNA maintained and manipulated in Escherichia coli. Between 13 and 23% of primary human CD3+, CD4+, CD8+, CD11b+, and CD19+ cells and more than 70% of CD4+ MT4 cells or various human tumor cell lines (MeWo, Huh7, HeLa, 293T, or H1299) could be transduced with one infectious unit of EHV-1 per cell. After intranasal instillation of EHV-1 into mice, efficient transgene expression in lungs was detectable. Successful immunization using EHV-1 was shown after delivery of the human immunodeficiency virus type 1 Pr55gag precursor by the induction of a Gag-specific CD8+ immune response in mice. Because EHV-1 was not neutralized by human sera containing high titers of antibodies directed against human herpesviruses 1 to 5, it is concluded that this animal herpesvirus has enormous potential as a vaccine vector, because it is able to efficiently transduce a variety of animal and human cells, has high DNA packaging capacity, and can conveniently be maintained and manipulated in prokaryotic cells. 相似文献
14.
Procario MC Levine RE McCarthy MK Kim E Zhu L Chang CH Hershenson MB Weinberg JB 《Journal of virology》2012,86(8):4194-4203
There is an incomplete understanding of the differences between neonatal immune responses that contribute to the increased susceptibility of neonates to some viral infections. We tested the hypothesis that neonates are more susceptible than adults to mouse adenovirus type 1 (MAV-1) respiratory infection and are impaired in the ability to generate a protective immune response against a second infection. Following intranasal infection, lung viral loads were greater in neonates than in adults during the acute phase but the virus was cleared from the lungs of neonates as efficiently as it was from adult lungs. Lung gamma interferon (IFN-γ) responses were blunted and delayed in neonates, and lung viral loads were higher in adult IFN-γ(-/-) mice than in IFN-γ(+/+) controls. However, administration of recombinant IFN-γ to neonates had no effect on lung viral loads. Recruitment of inflammatory cells to the airways was impaired in neonates. CD4 and CD8 T cell responses were similar in the lungs of neonates and adults, although a transient increase in regulatory T cells occurred only in the lungs of infected neonates. Infection of neonates led to protection against reinfection later in life that was associated with increased effector memory CD8 T cells in the lungs. We conclude that neonates are more susceptible than adults to acute MAV-1 respiratory infection but are capable of generating protective immune responses. 相似文献
15.
Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infiltrates after clearance of acute infection 总被引:4,自引:0,他引:4
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Podlech J Holtappels R Pahl-Seibert MF Steffens HP Reddehase MJ 《Journal of virology》2000,74(16):7496-7507
Interstitial pneumonia (IP) is a severe organ manifestation of cytomegalovirus (CMV) disease in the immunocompromised host, in particular in recipients of bone marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP include clinical evidence of pneumonia together with CMV detected in bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT and simultaneous infection of BALB/c mice with murine CMV for studying the pathogenesis of CMV-IP by controlled longitudinal analysis. A disseminated cytopathic infection of the lungs with fatal outcome was observed only when reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated an immunopathogenesis of acute CMV-IP. By contrast, after efficient hematolymphopoietic reconstitution, viral replication in the lungs was moderate and focal. The histopathological picture was dominated by preferential infiltration of CD8 T cells confining viral replication to inflammatory foci. Notably, after clearance of acute infection, CD62L(lo) and CD62L(hi) subsets of CD44(+) memory CD8 T cells were found to persist in lung tissue. One can thus operationally distinguish an early CMV-positive IP (phase 1) and a late CMV-negative IP (phase 2). According to the definition, phase 2 histopathology would not be diagnosed as a CMV-IP and could instead be misinterpreted as a CMV-induced immunopathology. We document here that phase 1 as well as phase 2 pulmonary CD8 T cells are capable of exerting effector functions and are effectual in protecting against productive infection. We propose that antiviral "stand-by" memory-effector T cells persist in the lungs to prevent virus recurrence from latency. 相似文献
16.
Emergence of CD8+ T cells expressing NK cell receptors in influenza A virus-infected mice 总被引:8,自引:0,他引:8
Kambayashi T Assarsson E Michaëlsson J Berglund P Diehl AD Chambers BJ Ljunggren HG 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(9):4964-4969
Both innate and adaptive immune responses play an important role in the recovery of the host from viral infections. In the present report, a subset of cells coexpressing CD8 and NKR-P1C (NK1.1) was found in the lungs of mice infected with influenza A virus. These cells were detected at low numbers in the lungs of uninfected mice, but represented up to 10% of the total CD8(+) T cell population at day 10 postinfection. Almost all of the CD8(+)NK1.1(+) cells were CD8alphabeta(+)CD3(+)TCRalphabeta(+) and a proportion of these cells also expressed the NK cell-associated Ly49 receptors. Interestingly, up to 30% of these cells were virus-specific T cells as determined by MHC class I tetramer staining and by intracellular staining of IFN-gamma after viral peptide stimulation. Moreover, these cells were distinct from conventional NKT cells as they were also found at increased numbers in influenza-infected CD1(-/-) mice. These results demonstrate that a significant proportion of CD8(+) T cells acquire NK1.1 and other NK cell-associated molecules, and suggests that these receptors may possibly regulate CD8(+) T cell effector functions during viral infection. 相似文献
17.
Byers AM Andrews NP Lukacher AE 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(10):6121-6129
Memory CD8 T cells comprise a critical component of durable immunity because of their capacity to rapidly proliferate and exert effector activity upon Ag rechallenge. During persistent viral infection, memory CD8 T cells repetitively encounter viral Ag and must maintain a delicate balance between limiting viral replication and minimizing immunopathology. In mice infected by polyoma virus, a natural mouse pathogen that establishes long-term persistent infection, the majority of persistence-phase antiviral CD8 T cells express the inhibitory NK cell receptor CD94/NKG2A. In this study, we asked whether CD94/NKG2A expression is associated with Ag-specific recall of polyoma virus-specific CD8 T cells. During the persistent phase of infection, polyoma virus-specific CD8 T cells that express CD94/NKG2A were found to preferentially proliferate; this proliferation was dependent on cognate Ag both in vitro and in vivo. In addition, CD94/NKG2A(+) polyoma-specific CD8 T cells have a markedly enhanced capacity to produce IL-2 upon ex vivo Ag stimulation compared with CD94/NKG2A(-) polyoma-specific CD8 T cells. Importantly, CD94/NKG2A(+) anti-polyoma virus CD8 T cells appear to be essential for Ag-specific recall responses in mice persistently infected by polyoma virus. Because of its higher proliferative potential and capacity to produce IL-2, we propose that the CD94/NKG2A(+) subpopulation represents a less differentiated state than the CD94/NKG2A(-) subpopulation. Identification of proliferation-competent subpopulations of memory CD8 T cells should prove valuable in designing therapeutic vaccination strategies for persistent viral infections. 相似文献
18.
N V Serbina V Lazarevic J L Flynn 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(12):6991-7000
The control of acute and chronic Mycobacterium tuberculosis infection is dependent on CD4(+) T cells. In a variety of systems CD8(+) T cell effector responses are dependent on CD4(+) T cell help. The development of CD8(+) T cell-mediated immune responses in the absence of CD4(+) T cells was investigated in a murine model of acute tuberculosis. In vitro and in vivo, priming of mycobacteria-specific CD8(+) T cells was unaffected by the absence of CD4(+) T cells. Infiltration of CD8(+) T cells into infected lungs of CD4(-/-) or wild-type mice was similar. IFN-gamma production by lung CD8(+) T cells in CD4(-/-) and wild-type mice was also comparable, suggesting that emergence of IFN-gamma-producing mycobacteria-specific CD8(+) T cells in the lungs was independent of CD4(+) T cell help. In contrast, cytotoxic activity of CD8(+) T cells from lungs of M. tuberculosis-infected mice was impaired in CD4(-/-) mice. Expression of mRNA for IL-2 and IL-15, cytokines critical for the development of cytotoxic effector cells, was diminished in the lungs of M. tuberculosis-infected CD4(-/-) mice. As tuberculosis is frequently associated with HIV infection and a subsequent loss of CD4(+) T cells, understanding the interaction between CD4(+) and CD8(+) T cell subsets during the immune response to M. tuberculosis is imperative for the design of successful vaccination strategies. 相似文献
19.
Mandl SJ Rountree RB Dalpozzo K Do L Lombardo JR Schoonmaker PL Dirmeier U Steigerwald R Giffon T Laus R Delcayre A 《Cancer immunology, immunotherapy : CII》2012,61(1):19-29
MVA-BN?-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN?-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occurred despite a strong tumor-mediated immunosuppressive environment characterized by a high frequency of regulatory T cells (T(reg)) in the lungs of tumor-bearing mice. Immunogenicity studies showed that treatment with MVA-BN?-HER2 induced strongly Th1-dominated HER-2-specific antibody and T-cell responses. MVA-BN?-HER2-induced anti-tumor activity was characterized by an increased infiltration of lungs with highly activated, HER-2-specific, CD8+CD11c+ T cells accompanied by a decrease in the frequency of T(reg) cells in the lung, resulting in a significantly increased ratio of effector T cells to T(reg) cells. In contrast, administration of HER2 protein formulated in Complete Freund's Adjuvant (CFA) induced a strongly Th2-biased immune response to HER-2. However, this did not lead to significant infiltration of the tumor-bearing lungs by CD8+ T cells or the decrease in the frequency of T(reg) cells nor did it result in anti-tumor efficacy. In vivo depletion of CD8+ cells confirmed that CD8 T cells were required for the anti-tumor activity of MVA-BN?-HER2. Furthermore, depletion of CD4+ or CD25+ cells demonstrated that tumor-induced T(reg) cells promoted tumor growth and that CD4 effector cells also contribute to MVA-BN?-HER2-mediated anti-tumor efficacy. Taken together, our data demonstrate that treatment with MVA-BN?-HER2 controls tumor growth through mechanisms including the induction of Th1-biased HER-2-specific immune responses and the control of tumor-mediated immunosuppression. 相似文献
20.
Starska K Głowacka E Kulig A Lewy-Trenda I Bryś M Lewkowicz P 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2011,49(4):593-603
One of the most important challenges in contemporary oncology is to find objective biomarkers of tumor aggressiveness, which help to identify more invasive phenotypes of the carcinoma. The purpose of this study was to investigate the relationships between the early and the late activation markers expression on T CD4(+) and CD8(+) cells subpopulations and certain clinicopathological characteristics of the neoplastic infiltration in order to determine their role as biomarkers for tumor behavior in squamous cell laryngeal carcinoma. Analysis of the early (CD69(+), CD71(+)) and the late activation antigens (CD25(+) (high), CD26(+), HLA/DR(+)) expression on T CD4+ and CD8(+) lymphocytes by cytofluorymetry in 55 patients treated for squamous cell laryngeal carcinoma was performed. Clinicomorphological analysis on the basis of TNM criteria and tumor front grading, which included tumor-related features and adjacent stroma-related characteristics of the peripheral edge of infiltration was carried out. The relationships between the activation markers expression and parameters of tumor aggressiveness were investigated. Our work revealed statistically significant differences in the expression of the studied activation markers on T cells with regard to certain clinicomorphological features. The expressions of CD69(+) and CD71(+) antigens on T CD3(+)CD4(+) and CD3(+)CD8(+) cells as well as CD4(+)HLA/DR(+) markers were higher for pT3 and pT4 tumors, in comparison with pT2 carcinomas. Moreover, tumors with the smallest number of TFG points were characterized by significantly lower values of the average expression of CD3(+)CD69(+) and CD3(+)CD71(+) as well as CD4(+)HLA/DR(+) markers on T lymphocytes. In addition, more aggressive and deeply infiltrating laryngeal carcinomas were most often characterized by significantly higher values of the average expression of CD69(+) and CD71(+) antigens on CD8(+) as well as HLA/DR(+) markers on CD4(+). Our study confirmed the implication of the early and the late activation antigens expression on CD4(+) and CD8(+) T lymphocytes in clinicomorphological parameters of the tumor, especially TFG total score and depth of invasion, and their importance as indicators of the invasive phenotype of laryngeal carcinoma. 相似文献