肠黏膜Th17细胞在HIV/AIDS病理过程中的作用

人类免疫缺陷病毒(Human immunodeficiency virus,HIV)主要利用CD4为受体、CCR5和CXCR4为辅助受体感染人CD4+T淋巴细胞,并在大多数感染者中引发获得性免疫缺陷综合征(acquired immunodeficiency syndrome,AIDS)[1].肠相关淋巴组织(gut-associated lymphoid tissue,GALT)具有丰富的CD4+ CCR5+T淋巴细胞,是HIV感染的主要靶组织.现已有研究表明,CD4+T细胞缺失和持续的免疫活化是HIV感染的主要免疫病理特征.病毒感染导致肠道免疫系统结构和功能的损伤、黏膜屏障破坏,从而导致机体慢性免疫活化,这可能是HIV-1致病的重要机制[2-3].     

HIV/AIDS患者肝组织HIV-1 p24抗原的免疫组化检测

目的　检测HIV抗原标志物在肝组织的表达情况,探讨HIV AIDS患者肝损伤发生的可能机制。方法　采用免疫组织化学方法对14例HIV AIDS患者的肝活检组织切片进行HIV 1p2 4抗原检测,比较不同病变肝组织中HIV 1p2 4抗原的表达数量。结果　在14例肝组织切片的Kupffer细胞、内皮细胞、肝细胞均发现HIV 1p2 4抗原表达;阳性肝细胞计数分析显示,表达数量随病变严重程度而增加(P <0 0 5 )。结论　HIV能够在HIV AIDS患者的肝脏内表达,并且可能参与肝细胞的凋亡。     

Th1和Th17细胞在活动期肺结核病患者外周比例失衡的临床研究

结核病是全球性严重危害人类健康的传染性疾病之一,深入解析结核分枝杆菌(Mycobacterium tuberculosis,Mtb)感染过程中宿主免疫应答特征是研发和评价有效的结核疫苗的重要前提。本研究以Th1、Th17和Th22细胞免疫应答为切人点,检测抗原特异性和非特异性活化后的Th1、Th17和Th22型细胞因子分泌细胞的比例。结果显示,和正常人群相比,结核病患者的T细胞在非特异性刺激下的Th1型细胞免疫应答能力明显高于健康人,即分泌IFN-γ和TNF-α的细胞数量明显增多,但IL-17型应答能力则低于健康人群;经M.tb特异性抗原ESAT6-CFP10刺激后,活动期肺结核病患者分泌IFN-γ的T细胞比例高于健康人,而分泌TNF-α的T细胞的比例与健康人相比却显著下降,分析Th1型与Th17型细胞之比显示结核病患者要高于健康人,而Th22型细胞应答在活动期结核病患者中的水平和正常人群相近。上述研究结果显示活动性肺结核病患者外周Th1型和Th17型细胞和正常人相比存在应答失衡,这一比例失调有望为评价结核疫苗效果和抗结核免疫应答的免疫学特征提供新依据。     

Th1样Th17细胞在自身免疫性疾病中的研究进展

辅助性T细胞17(Th17)具有高度可塑性,在一定炎症环境下可分化为主要表达γ干扰素(IFN-γ)的Th1样Th17细胞(CCR6+CXCR3+).目前认为,这些Th1样Th17细胞是自身免疫性疾病的主要致病细胞.本文就Th1样Th17细胞的生物学特性、分化机制及其在自身免疫性疾病发展和发病机制中的作用进行综述,旨在为...     

HLA多态性与HIV感染及AIDS发病相关性的研究

为研究人类白细胞抗原（ＨＬＡ）和人免疫缺陷病毒（ＨＩＶ）易感性的关系，本文分析比较了以下三组人群的ＨＬＡ表型频率和单倍型频率：①１７２例正常人；②１７例血清ＨＩＶ阴性高危人群；③１８０例血清ＨＩＶ阳性患者，其中２１例发展为艾滋病（ＡＩＤＳ），３７例６个月内ＣＤ４＋淋巴细胞降低至少２０％（ＣＤ４ｄｅｃｌｉｎｅ）。在１７２例对照和１８０例血清ＨＩＶ阳性受试者的比较中发现，其ＨＬＡ表型频率和单倍型频率没有显著差别，提示ＨＩＶ感染与ＨＬＡ无关联。然而，ＨＬＡ－Ｂ２１、ＨＬＡ－Ｂ８、ＨＬＡ－Ｂ３５表型及ＨＬＡ－Ａ１－Ｂ８、ＨＬＡ－Ｂ８－ＤＲ３、ＨＬＡ－Ａ１－Ｂ８－ＤＲ３单倍型与ＣＤ４阳性淋巴细胞下降，或与血清ＨＩＶ感染发展成ＡＩＤＳ病显著相关。１７例ＨＩＶ血清阴性高危人群中，无一携带单倍型ＨＬＡ－Ａ１－Ｂ８－ＤＲ３，提示该单倍型可能与ＨＩＶ感染的抗性相关。     

Th17细胞与Th1、Treg细胞关系的研究进展

CD4~+T细胞在不同细胞因子环境中可分化为Th1、Th2、Treg、Th17四种亚群,在一定条件下,各Th细胞亚群之间可以互相转化,从而使机体的免疫效应和免疫抑制处于精细而复杂的平衡状态。Th17细胞与自身免疫性疾病和肿瘤的发生发展关系密切,研究Th17细胞与Th1细胞、Treg细胞之间的相互关系,对于预防和治疗自身免疫性疾病和肿瘤等临床难题意义重大。     

Th1／Th2与慢性乙型肝炎

慢性乙型肝炎发病机制复杂，与机体的免疫状态密切相关，CD4^ Th细胞是机体的重要调节细胞，根据其产生细胞因子的不同分为Th1和Th2亚型，分别参与调节细胞免疫和体液免疫，Th1和Th2可相互调节，影响免疫应答的格局，Th1／Th2在多种感染性疾病中发挥重要作用，慢性乙肝患者存在Th1／Th2失衡，本文就Th1／Th2与慢性乙肝的关系研究进展进行简述。     

支气管哮喘患者外周血Th17 与Th9 细胞的变化及临床意义

目的:探讨Th17、Th9 细胞水平在支气管哮喘患者中的表达及其临床意义。方法:选取67 例哮喘患者为研究对象,30 例健康体检者为对照组,根据全球哮喘防治倡议(GINA)将哮喘患者分为间歇与轻度持续组20 例,中度持续组25 例和重度持续组22 例。收集患者临床资料,完成哮喘控制测试(ACT)评分、肺功能和呼出气一氧化氮(FeNO)值测定,流式细胞仪检测外周血PBMC 中CD3+ CD8- IL-17+ 、CD3+ CD8- IL-9+细胞水平。结果:与健康对照组相比,哮喘患者Th17、Th9 细胞水平均明显升高(P<0.05);中重度哮喘患者Th17 及Th9 细胞水平显著高于间歇与轻度哮喘组(P<0.05),而间歇与轻度哮喘组患者与健康对照组比较,差异无统计学意义(P>0.05)。哮喘患者外周血Th17 及Th9 细胞的表达均与FeNO 值正相关(r 值依次为0.501、0.438;P<0.05),与ACT 评分、肺功能FEV1、FEV1/ FVC 及PEF 负相关(r 值依次为-0.441、-0.362;-0.307、-0.377;-0.419、-0.411;-0.428、-0.24;P<0.05),同时Th17 与Th9 细胞在哮喘患者外周血中的表达率正相关(r 值为0.443,P<0.05)。结论:Th17、Th9 细胞在哮喘患者中高表达,具有协同致炎作用,且与症状严重程度相关,提示Th17 及Th9 细胞对哮喘患者病情评估有潜在的参考价值。     

鼻息肉患者外周血Th17/Treg细胞比率的失衡及其临床意义

目的:观察鼻息肉(NP)患者外周血Th17和Foxp3+ CD4+ CD25+调节性T细胞(Treg)的水平及其与临床病情的关系,初步探讨Th17/Treg细胞的比率失衡在NP发病机制中的作用和意义.方法:NP患者根据鼻内镜和鼻窦CT评分的结果分为1组(鼻内镜检查评分:2～8分;CT检查评分:3～10分,n=23)和2组(鼻内镜检查评分:8～12分;CT检查评分:10～19分,n=23),选取10例单纯鼻中隔偏曲患者作为对照组.采用流式细胞术检测外周血中Th17和Treg的比例,并对Th17/Treg的比率及鼻内镜、鼻窦CT评分进行相关性分析.结果:两组NP患者外周血中Th17细胞比率明显高于对照组(P＜0.01),且2组高于1组(P＜0.05).两组NP患者外周血中Treg细胞的比率明显低于对照组(P＜0.01),但两组间差异无统计学意义.两组NP患者Th17/Treg细胞的比率明显高于对照组(P＜0.01),且两组间差异显著(P＜0.05).同时,相关性分析结果显示,Th17/Treg细胞的比率与鼻内镜、鼻窦CT评分呈正相关(r=0.562,r=0.667,P＜0.01).结论:NP患者外周血中Th17细胞比率增加和Treg细胞比率降低所致的Th17/Treg细胞比率失衡,可能在NP的发生发展中起着重要作用.Th17/Treg比率失衡的程度可能与临床病情严重程度密切相关.     

急性冠脉综合征患者Th17和Treg细胞的检测及意义

目的:探讨急性冠脉综合征患者Th17细胞和Treg细胞的变化及意义。方法:选取51例急性冠脉综合征患者,25例稳定性心绞痛(SA)患者,27例同期住院的健康对照者,分别采用流式细胞术、实时定量PCR和ELISA法检测外周血Th17细胞和Treg细胞百分率、关键核转录因子RORγt、STAT3和Foxp3 mRNA的表达以及血浆IL-17A和TGF-β1的浓度。结果:①ACS患者外周血中Th17细胞百分率、RORγt和STAT3 mRNA显著高于SA患者和对照组(P<0.01);②与SA组和对照组相比,ACS患者CD4+CD25+Foxp3+Treg和CD4+Foxp3+Treg细胞百分率,Foxp3 mRNA的表达以及血浆TGF-β1的浓度显著降低(P<0.01)。结论:ACS患者外周血中Th17/Treg失衡,Th17/Treg失衡可能与斑块的不稳定密切相关。     

湖南艾滋病患者Th17和Tr细胞及IL-17在抗病毒治疗过程中的变化

目的 观察HIV感染者和AIDS患者血IL-17、CD3+CD4+IL-17+细胞(Th17细胞)和CD4+CD25+Foxp3+T细胞(Tr细胞)的平衡状态及其在1年高效抗反转录病毒治疗(HAART)中的变化.方法 选取经HAART治疗的HIV/AIDS患者33例,同时选取33例健康志愿者为对照,分别于治疗0、6、12个月采集静脉血,检测血清IL-17水平、Th17细胞及Tr细胞百分比,并对比分析其相互关系.结果 HIV/AIDS在HAART治疗前、治疗6个月、12个月及健康对照外周血的Th17细胞在CD4+T细胞中的比例分别为(1.20±0.37)%、(2.50±1.03)%、(3.70±1.56)%和(4.70±1.43)%;Tr细胞在CD4+T细胞中的比例分别为(9.16±3.33)%、(7.19±2.91)%、(5.53±1.88)%和(4.43±0.97)%;血清IL-17水平分别为(5.3±2.5) pg/ml、(7.7±2.4) pg/ml、(10.4±3.1) pg/ml和(17.7±6.6) pg/ml.Th17细胞水平与CD4+T细胞计数正相关,与病毒载量负相关;Tr细胞水平与CD4+T细胞计数负相关,与病毒载量正相关.结论 HIV感染导致IL-17、Th17细胞和Tr细胞的失平衡,而HAART治疗可能逐渐恢复二者的免疫平衡状态.提示三者可能在艾滋病发病机制中起作用,并有可能成为观察艾滋病进展和HAART治疗效果的有效指标.

Abstract：

Objective To observe the Th17, IL-17 and Tr cells equilibrium state as well as their changes of HIV infected or AIDS suffered patients in one-year HAART treatment. Methods Select 33 HIV/AIDS patients received HAART treatment while 33 healthy volunteers as controls. Flow cytometry was used to analyze Th17 and Tr cells in venous blood at the time of pre-therapy, 6th, 12th month when IL-17 levels in serum are tested by ELISA. Results The ratio of Th17 cells in CD4 cells in HIV/AIDS patients and volunteers were (1.20±0.37)%, (2.50±1.03)%, (3.70±1.56)%, (4.70±1.43)%, respectively; The ratio of Tr cells were (9.16±3.33)%, (7.19±2.91)%, (5.53±1.88)%, (4.43±0.97)%, respectively; The levels of IL-17 in serum were (5.3±2.5) pg/ml, (7.7±2.4) pg/ml, (10.4±3.1) pg/ml, (17.7±6.6) pg/ml respectively. The Th17 cells' level was positively correlative with the amount of CD4 cells, negatively correlate with the count of viral load. However, the Tr cells level is positively correlative with the count of viral load, negatively relate to the quantity of CD4 cells. Conclusion HIV could make IL-17, Th17 cells and Tr cells lost their balance, but the immune equilibrium state may gradually recover after HAART treatment. Which indicates the IL-17, Th17 cells and Treg cells may play an important role in the pathogenesis of AIDS, and they are likely to be the effective indexes to observe the progress of AIDS and the treatment effect of highly active antiretroviral therapy(HAART).     

Lipid profile in HIV/AIDS patients in Nigeria

Introduction

Alterations of serum lipid profiles have been reported widely among Human Immuno deficiency Virus (HIV) positive patients on Highly Active Anti Retroviral Therapy (HAART). However, there are few data on serum lipid profile among treatment naïve HIV positive patients in our environment.

Objectives

To describe the pattern of lipid profile among treatment naïve HIV positive patients and changes following HAART initiation.

Methods

One hundred and thirty HIV positive patients seen in HIV center in an urban area in Nigeria and 44 matched individuals were recruited. Data were collected on socio demographic characters, baseline lipid profiles and CD4 count. Values of lipid parameters were retrieved after 12 months on HAART.

Results

The mean Low density lipoprotein(LDL) was 2.26+ 0.9 mmol/l among the test group compared with 0.96+0.39mmol/L among the control, p value=0.000. The mean High density lipoprotein (HDL) was also significantly lower, 0.8+0.6mmol/L reaching a dyslipidemic level, in the HIV positive group than the control, p value = 0.00. Tuberculosis/HIV co infected patients had a significantly elevated mean LDL, p=0.002.

Conclusion

Abnormality of serum lipid is common among treatment naïve HIV patients seen in Nigeria. The NNRTI regimen is associated with elevation of HDL and some stabilization of TC and TG.     

艾滋病与咨询

1　艾滋病流行概况艾滋病 (ＡＩＤＳ)是人类免疫缺陷病毒 (ＨＩＶ )引起的、通过性、血液和围产期母婴三种途径传播的传染病。根据联合国艾滋病规划署 (ＵＮＡＩＤＳ)和世界卫生组织 (ＷＨＯ) 1999年 12月公布的数据 ,自艾滋病流行以来 ,全世界累计已有 1880万人死于艾滋病 ,目前存活的艾滋病毒感染者和艾滋病人估计为 3430万[1] 。艾滋病已成为世界上仅次于心脏病、脑卒中和急性下呼吸道感染的第四个主要死因 ,是造成死亡最多的传染病 ,它已成为发展中国家主要的疾病负担[2 ] 。艾滋病流行对社会、经济和人口方面的毁灭性冲击是独一无二的[…     

Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques

Loss of CD4⁺ T cells in the gut is necessary but not sufficient to cause AIDS in animal models, raising the possibility that a differential loss of CD4⁺ T-cell subtypes may be important. We found that CD4⁺ T cells that produce interleukin (IL)-17, a recently identified lineage of effector CD4⁺ T-helper cells, are infected by SIV_mac251in vitro and in vivo, and are found at lower frequency at mucosal and systemic sites within a few weeks from infection. In highly viremic animals, Th1 cells predominates over Th17 T cells and the frequency of Th17 cells at mucosal sites is negatively correlated with plasma virus level. Because Th17 cells play a central role in innate and adaptive immune response to extracellular bacteria, our finding may explain the chronic enteropathy in human immunodeficiency virus (HIV) infection. Thus, therapeutic approaches that reconstitute an adequate balance between Th1 and Th17 may be beneficial in the treatment of HIV infection.     

HIV/AIDS患者外周血T淋巴细胞亚群的研究

目的 通过对HIV/AIDS患者外周血T淋巴细胞亚群进行分析,探讨初始、记忆和效应T细胞各亚群的变化情况及其与疾病进展的关系.方法 应用流式细胞仪检测15例正常人,79例HIV/AIDS患者CD4<200组17例、200≤CD4≤500组45例和CD4>500组17例.外周血淋巴细胞中T细胞各亚群绝对数及百分比.结果随着疾病进展,CD4+ 初始细胞(Naive)计数和比例均逐渐减少(P<0.001);CD4+中枢性记忆T细胞(Tcm)计数逐渐降低(P<0.001),但百分比逐渐升高(P=0.002);CD4+效应记忆性T细胞(TEMA)百分比上升(P<0.001);CD8+Naive细胞计数及百分比均逐渐下降(P<0.05);CD8+ TCM、TEM和终末分化的效应性记忆T细胞(TEMRA)的计数及百分比,各组间差异均无统计学意义(P>0.05).结论 HIV感染者外周血T淋巴细胞亚群发生显著变化,幼稚型T淋巴细胞数目逐渐减少,功能型T淋巴细胞数目增加.本研究有助于对HIV致病机制的研究及疾病进展的监测.     

HIV／TB重叠感染者HAART治疗前后Th17／Treg免疫调节的初步研究

目的初步探讨HIV／TB重叠感染者在高抗逆转录病毒治疗（HAART）治疗前后Th17／Treg的免疫调节作用。方法HIV／TB重叠感染者（HIV／TB组）10例和单纯HIV感染者（HIV组）10例分别接受HAART治疗,应用流式细胞术分析患者HAART治疗前和治疗后1个月的外周血Th17和CD4＋CD25＋调节性T细胞（Treg）细胞表型。结果HIV／TB组IL-17＋CD4＋T细胞的百分率在治疗前后分别为1．90％±0．9％和4．65％±1．48％,HIV／TB组在治疗后较治疗前IL—17＋T细胞升高,差异有统计学意义（P〈0．01）;HAART治疗前后IL-17的百分率差值在HIV／TB组与HIV组中分别为2．65％±1．62％,0．67％±0．46％,HIV／TB组治疗后IL-17＋T的上升速度显著高于单纯HIV感染组（P〈0．01）。HIV／TB组Treg的百分率在治疗前后分别为16．48％±4．91％,8．29％±3．13％,治疗前后差异有统计学意义（P〈0．01）;治疗前后Treg的百分率差值在HIV／TB组与HIV组中分别为8．91％±4．82％,2．63％±2．34％,HIV／TB组治疗后Treg下降速度高于HIV组,差异有统计学意义（P〈0．01）。结论TB和HAART治疗均影响Th17／Treg的免疫应答,Th17表达上调,促炎作用增强,Treg表达下调,抑炎作用减弱,而且HIV／TB重叠感染者在HAART治疗过程中更容易出现Th17／Treg平衡紊乱,可能与HAART治疗后出现结核性免疫重建综合征有相关性。     

Loss of the balance between CD4Foxp3 regulatory T cells and CD4IL17A Th17 cells in patients with type 1 diabetes

The presence of low-grade chronic inflammation is a known feature of long standing diabetes type 1. Recently, two T cell subsets, that may contribute to the disease progression are under investigation. These are Treg cells, which are specialized T cell subset, that controls the activity of autoreactive and inflammatory cells and Th17 cells which are involved in the pathogenesis of inflammatory and autoimmune diseases. The balance between Treg and Th17 controls inflammation and is responsible for the proper function of the immune system. An decrease of Tregs and/or increase of Th17 may induce local inflammation, which in turn may hasten the development of diabetic complications. In the present study, we have demonstrated that the Treg/Th17 balance was broken in patients with diabetes type 1 and might contribute to the progression of microvascular angiopathy.     

210例HIV/AIDS患者淋巴细胞计数与机会性感染相关分析

目的分析HIV/AIDS患者总淋巴细胞计数（TLC）与机会性感染的关系,为HIV/AIDS患者机会性感染的治疗及一级、二级预防提供参考依据。方法对2009年6月至2011年5月210例HIV/AIDS患者的淋巴细胞及出现的机会性感染进行分析。将患者分为TLC〉1300个/μl组（G1组）和TLC≤1300个/μl组（G2组）,比较两组患者机会性感染发生率的差异。结果 210例HIV/AIDS患者机会性感染的总感染率为86.7%,主要的机会性感染为口腔念珠菌感染（56.2%）、细菌性肺炎（46.7%）、肺结核（42.4%）、败血症（21.4%）、感染性腹泻（20.5%）。G2组患者机会性感染的发生率为93.6%,高于G1组患者（55.3%）,差异有统计学意义（P〈0.05）;随着TLC的下降,患者发生机会性感染的机率增高。结论 HIV/AIDS患者机会性感染的发生率高,TLC是HIV/AIDS患者发生机会性感染的独立危险因素。因此,应定期监测HIV/AIDS患者TLC,加强患者机会性感染的一级和二级预防。     

Mycoplasmas infection in male HIV/AIDS patients in Jiangsu,China

Mycoplasmas are widely distributed among animals, plants, and human. The four species namely, Mycoplasmas genitalium(Mg), Mycoplasmas fermentans(Mf), Mycoplasmas pentrans(Mpe), Mycoplasmas pirum(Mpi) are also called AIDS-associated mycoplasmas due to their involvement in the development and outcome of AIDS. To investigate the infection prevalence of Mg, Mf, Mpe and Mpi among male HIV/AIDS patients in Jiangsu Province and to analyze the relationship between pathogenic mycoplasmas and cellular immune function of them. First void urine and venous blood samples were collected and epidemiology questionnaires were administered after informed consent. Nested PCR was performed to determine the infection of Mg, Mf, Mpe and Mpi while ELISA assay was applied to detect interleukin-2(IL-2), interferon-γ(IFN-γ) and tumor necrosis factor-α(TNF-α). SAS 9.0 software was applied to analyze the data. A total of 713 HIV/AIDS patients were recruited in this study. The overall infection rates of Mg, Mf, Mpe and Mpi are 27.9%, 9.7%, 1.0% and 18.4% respectively. Generally, the infection rates of Mg(χ² = 10.311, P = 0.006) and Mpi were declined as the CD4+ cell counts increased, while Mf infection was higher in CD4+ T cell>350/μl group. The levels of cytokines are different with the variance of mycoplasmas infection. Mycoplasma infection among male HIV/AIDS patients is associated with changes in cellular immune response (cytokines). However, the affect of mycoplasmas on the immune function is complex, further studies are still required to elucidate whether mycoplasmas interact with HIV by interfering host immune system.