中国HIV-1感染者病毒特异性细胞毒性T细胞定量研究

目的对8例HIV长期感染不进展(LTNP)及病程进展缓慢(SP)患者的病毒特异性细胞毒性T细胞(CTL)特征进行研究。方法设立队列研究,从中随机选出8例患者(4例LTNPs,4例SP)。通过采用重叠肽技术组建HIV-1B亚型全序列肽段,组建成三维肽库进行ELISPOT分析8例患者的HIV-1特异性细胞免疫反应。结果在大多数患者中存在较强的T细胞反应,特别对HIV-1病毒的pol、gag、nef蛋白的免疫反应比其他蛋白强。结论病毒特异性CTL免疫反应在HIV-1 LTNPs有较强并且很广泛的反应,这对于有效抑制病毒在人体内的生存有可能起到很大的作用,很可能是这些LTNPs及SP病程进展缓慢的主要原因之一。     

人类免疫缺陷病毒1 Gag-特异性T淋巴细胞增殖反应特征的研究

目的了解人类免疫缺陷病毒（HIV）感染者HIV-1Gag-特异性T淋巴细胞增殖反应特征,分析它们与疾病进展的关系,探讨HIV特异性免疫功能缺陷的发生机制。方法采用BrdU掺入的流式细胞仪胞内染色法,检测34例HIV-1感染者PBMC对HIV-1Gag抗原的特异性增殖反应频率,分析它们与CD4^＋T细胞绝对值、血浆病毒载量及CD8^＋T细胞活化指标的相关性。结果HIV感染者HIV-1Gag．特异性CD4^＋T细胞增殖率显著低于健康对照组（P〈0．01）,与CD8^＋T细胞CD38表达负相关（P〈0．01）,与CD4绝对值正相关（P〈0．01）,与血浆病毒载量负相关（P〈0．05）;中国HIV感染者HIV-1 Gag-特异性CD8^＋T细胞增殖率显著高于健康对照组（P〈0．01）,与CD8^＋T细胞CD38表达正相关（P〈0．01）,与CD4绝对值显著负相关（P〈0．01）,与血浆病毒载量不相关（P〉0．05）。结论HIV感染者T细胞增殖功能异常,HIV-1Gag-特异性CD4^＋T细胞增殖功能减低,其程度与疾病进展密切相关。     

HIV感染者和AIDS患者外周血T淋巴细胞活化亚群与病毒载量的相关性分析

目的探讨人类免疫缺陷病毒(HIV)感染者和艾滋病(AIDS)患者外周血T淋巴细胞活化亚群与病毒载量的相关性。方法选取2013年2月至2016年8月郑州市第六人民医院收治的49例HIV感染者及AIDS患者,根据疾病类型分为HIV组与AIDS组。入院后均抽取患者空腹外周静脉血分离送检,采用FACS Calibur流式细胞仪对T淋巴细胞亚群CD3~+、CD4~+、CD8~+进行计数,并计算CD4~+/CD8~+比值,以全自动病毒载量仪检测HIV病毒载量。结果 HIV组CD3~+、CD4~+数目多于AIDS组,CD4~+/CD8~+水平高于AIDS组,HIV RNA载量小于AIDS组,差异有统计学意义(P<0.05);HIV RNA载量水平与CD3~+无相关性,差异无统计学意义(P>0.05),与CD4~+、CD4~+/CD8~+呈负相关,差异有统计学意义(P<0.05)。结论 HIV感染者与AIDS患者外周血T淋巴细胞活化亚群CD4~+、CD4~+/CD8~+与病毒载量呈负相关,随病毒载量水平升高,患者免疫功能亦会明显下降。     

慢性乙肝患者的免疫状态与病毒载量及抗病毒疗效的关系研究

目的 探讨慢性乙肝(chronic hepatitis B,CHB)患者的机体免疫状态与病毒载量及抗病毒疗效的关系.方法 将237例CHB患者按照乙肝病毒(hepatitis B virus,HBV)载量,分为病毒阴性组、低病毒载量组和高病毒载量组,比较各组的免疫球蛋白、补体及T细胞亚群等免疫指标的差异.对其中符合抗HBV治疗指征的患者给予抗HBV治疗,观察治疗半年后的病毒学应答情况和治疗1年后的e抗原血清学应答情况,分析初始免疫状态与抗病毒疗效的关系.结果 随着HBV-DNA载量的升高,CHB患者的CD3+、CD4+及CD8+T细胞计数随之升高,而CD4+/CD8+比值随之下降(P＜0.05).完全病毒学应答组和部分/无病毒学应答组的初始免疫指标比较,差异无统计学意义(P＞0.05).获得e抗原血清学转换者与未获得e抗原血清学转换者相比,在开始抗病毒治疗时的ALT和AST水平更高(P＜0.05),但初始免疫指标差异无统计学意义(P＞0.05).结论 CHB患者的免疫状态与HBV-DNA载量相关,CD3+、CD4+及CD8+T细胞计数随着HBV-DNA载量的升高而升高,而CD4+/CD8+比值则随之下降.CHB患者在抗病毒治疗时的初始免疫状态与病毒学应答及e抗原血清学转换无明显相关性.     

体内CD8~+T细胞剔除对无症状期SHIV感染猴的影响

目的 CD8+T细胞在一些病毒感染疾病的免疫反应中起着重要的作用,但CD8+T细胞在HIV无症状期的作用尚不明确,本研究通过体内CD8+T细胞剔除,研究CD8+T细胞对SHIV感染猴的影响,进一步了解艾滋病的发病机制。方法选择8只SHIV病毒感染的恒河猴,均处于无症状期,随机分成两组,实验组4只恒河猴在0、3、7 d注射抗CD8+T抗体cM-T807,不同的时间取外周血、腹股沟淋巴结。流式细胞术测定恒河猴外周血和淋巴结中CD8+T细胞数目,Real-time RT-PCR法测定实验猴血浆病毒载量,并使用IFN-γElispot方法测定其对猴细胞免疫的影响。结果 CD8+T细胞敲除后,4只猴的病毒载量都转阳,但反应性不一,HIV-1的靶细胞CD4+T细胞有轻微下降,后反弹,与病毒载量无相关性;CD8敲除猴的感染情况(血浆病毒载量和CD4细胞)比SHIV病毒急性感染轻,这与ELIPOT结果一致。结论 CD8+T细胞在HIV无症状期发挥重要的作用,但其作用具有个体差别。     

HIV／AIDS合并HBV／HCV感染病毒载量水平及与T淋巴细胞相关性的探讨

目的：探讨人类免疫缺陷病毒（HIV）／艾滋病（AIDS）合并乙型肝炎病毒（HBV）／丙型肝炎病毒（HCV）感染后病毒载量水平变化及对机体T淋巴细胞免疫机制的影响。方法分别测定 HIV／AIDS单纯感染组,HIV／HBV合并感染组,HIV／HCV合并感染组3组的 HIV RNA、HBV DNA、HCV RNA、CD4＋ T淋巴细胞频数、CD8＋ T淋巴细胞频数、CD4／CD8比值,并分析各组T淋巴细胞与HIV RNA的关系,HBV DNA／HCV RNA与HIV RNA、CD4＋ T淋巴细胞、CD8＋ T淋巴细胞、CD4／CD8比值的相关性。结果 HIV／AIDS单纯感染组、HIV／HBV合并感染组及 HIV／HCV合并感染组的CD4＋ T 淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义（P＜0．05）;HIV／AIDS单纯感染组、HIV／HBV合并感染组的CD8＋ T淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义（P＜0．05）;HIV／AIDS单纯感染组、HIV／HBV合并感染组及 HIV／HCV合并感染组的CD4／CD8与各自组的HIV RNA呈负相关,差异有统计学意义（P＜0．05）。结论合并感染 HBV后,HIV／AIDS患者T细胞的数量下降更明显,致HIV RNA、HBV DNA高载量,加速了 HIV病情进展;感染 HBV后CD4＋ T细胞的数量下降比感染HCV更明显。     

HIV-1感染者CD8~+T细胞表面PD-1表达水平的研究

目的探索我国HIV感染者CD8+T细胞表面PD-1表达水平及其与疾病进展的关系。方法运用流式细胞术测定72例HIV-1感染者和29例健康对照外周血CD8+T细胞表面PD-1表达水平,分析PD-1表达水平与HIV感染者CD4+T细胞计数和血浆病毒载量的相关性。结果 HIV感染者外周血CD8+T细胞表面PD-1表达水平显著高于健康对照(30.395%vs 18.450%,P=0.001),且与CD4+T细胞计数负相关(r=-0.401,P0.001),与病毒载量正相关(r=0.247,P=0.0368);CD4+T细胞计数小于200细胞/μl的感染者CD8+T细胞表面PD-1表达水平显著高于CD4+T细胞计数大于500细胞/μl的感染者(P=0.002);PD-1的表达在新发感染期和艾滋病期出现两个高峰;长期不进展者PD-1的表达水平与正常对照组差别无统计学意义。结论 HIV感染可显著上调CD8+T细胞表面PD-1的表达水平,PD-1表达水平的变化与HIV疾病进展密切相关。     

HIV/AIDS患者与HBV、HCV共感染对外周血病毒载量及T淋巴细胞亚群表达影响的相关性分析

目的:分析HIV/AIDS患者与HBV、HCV共感染对外周血病毒载量及T淋巴细胞亚群表达水平影响的相关性。方法:采用流式细胞术及PCR法对115例HIV单独感染者、HIV/HBV、HIV/HCV及HIV/HBV/HCV合并感染者外周血的CD4+T细胞、CD8+T细胞表达水平、CD4+T/CD8+T细胞比值、HIV RNA、HBV DNA及HCV RNA病毒载量进行比较分析。结果:HIV与HBV、HCV共感染者的肝功能异常、肝衰竭及死亡发生率均随着CD4+T细胞表达水平下降而增加,其三组间比较差异有统计学意义(P<0.05);在HIV组、HIV/HBV组、HIV/HCV组、HIV/HBV/HCV 4组间CD4+T细胞计数与CD8+T细胞计数两组间比较差异有统计学意义(P<0.05),HIV单独感染者的CD8+T细胞数与不同类型的HIV/HBV、HIV/HCV、HIV/HBV/HCV共感染组间比较,除HIV/HBV共感染组与HIV/HCV共感染组比较差异无统计学意义(P>0.05),其余每二组间比较差异均有统计学意义(P<0.05);HIV组、HIV/HBV组、HIV/HCV组、HIV/HBV/HCV共感染组的CD4+T淋巴细胞、CD8+T淋巴细胞与各自组的HIV RNA载量比较呈负相关系(P<0.05)。结论:HIV合并HBV、HCV感染会影响外周血T淋巴细胞表达水平及生物学功能,降低对病毒的清除作用,促进HIV-RNA复制,加速HIV/AIDS的免疫损伤,从而加速疾病进程。     

13例艾滋病患者HAART后HIV-RNA变化与CD4变化的关系分析

目的 探讨高效抗逆转录病毒治疗（highly active antiretroviral therapy，HAART）后艾滋病患者HIV—RNA病毒载量变化与CD4淋巴细胞计数变化的相关性。方法 选择2004年在我院接受HAART的艾滋病患者13例，观察HAART后HIV—RNA载量的变化情况，以及CD4细胞的变化情况，进而分析二者的相关性。结果 13例患者中有12例（92．3％）接受HAART后，在HIV—RNA载量下降的同时伴CD4细胞缓慢攀升。结论 HAART后，艾滋病患者的HIV—RNA载量变化与CD4细胞变化呈良好的负相关，随着病毒载量的下降，CD4细胞逐渐上升。     

艾滋病患者结核杆菌感染与其免疫功能及HIV载量的关系

目的:探讨艾滋病(AIDS)患者结核杆菌感染与其免疫功能及艾滋病病毒(HIV)载量的关系。方法:选取2018年6月至2020年1月浙江大学医学院附属湖州医院湖州市中心医院感染科收治的78例AIDS患者作为研究对象,所有患者入院后均完成首段尿、静脉血等样本采集,采用培养法和PCR法检测结核杆菌。根据患者是否发生感染分为观察组(n=38)和对照组(n=40)。采用流式细胞仪测定两组CD4^(+)免疫功能水平;采用病毒载量分析仪测定两组HIV载量;对AIDS结核杆菌感染与患者免疫功能及HIV载量进行相关性分析,分析AIDS患者的结核杆菌感染类型及构成比、两组AIDS患者结核杆菌感染下CD4^(+)T细胞水平、细胞因子水平、HIV载量,并完成结核杆菌感染与其免疫功能及HIV载量关系分析。结果:38例伴有结核杆菌感染AIDS患者,排在前两位的分别为肺结核和颈淋巴结核,分别占36.84%和28.95%;观察组结核杆菌感染患者CD4^(+)T细胞中<50mm^(3)、50－199mm^(3)病例数高于对照组非感染者(P<0.05);200－349mm^(3)、≥350mm^(3)病例数低于对照组非感染者(P<0.05);观察组HIV载量中<1000 copy/ml、1000－4999 copy/ml病例数低于对照组(P<0.05);≥10000 copy/ml病例数高于对照组(P<0.001);相关性分析结果表明,AIDS患者结核杆菌感染率与患者免疫功能CD4^(+)T水平呈负相关(P<0.05);与HIV载量呈正相关(P<0.05)。结论:结核杆菌感染能影响AIDS患者免疫功能,且与HIV载量存在相关性,积极采取有效的措施能提高机体免疫,对降低结核杆菌感染率具有重要的意义。     

HIV-Specific IL-2+ and/or IFN-γ+ CD8+ T Cell Reponses during Chronic HIV-1 Infection in Former Blood Donors

Objective Conflicting data have been generated from previous studies to determine which kind of relationship exists between HIV-1 specific CD8 T-cell responses and HIV-1 viral load or CD4 count over the course of infection.In this study,153 HIV-1 infected LTNPs were enrolled to investigate the role of HIV-1 specific CD8 T-cell responses in chronic HIV-1 infection among HIV-1 infected former blood donors.Methods The patients were stratified into three groups according to CD4 count:CD4≥500 cells/μL; 350 cells/μL≤CD4<500 cells/μL; CD4<350 cells/μL.PBMCs were isolated from the patients' anticoagulated blood samples.IL-2 and IFN-γ secretions of CD 8 T cells against 17 HIV-1 consensus B full peptide pools were analyzed by using ICS assay.Results An overall inverse correlation were observed between CD4 count and plasma viral load.Although no significant difference was observed during the comparisons of frequency/breadth of HIV-1 specific CD8 T cell responses,CD4 count stratification analysis showed that different correlation pattern existed in three strata: as for patients whose CD4 counts were less than 350 cells/μL,no significant correlations were identified between frequency/breadth of HIV-1 specific CD8 T cell responses and CD4 count/viral load; as for patients whose CD4 counts ranged from 350 cells/μL to 500 cells/μL,significant correlation was only observed between the response breadth of IL-2+IFN-γ+CD8 T cells and CD4 count; however,as for patients whose CD4 counts were more than 500 cells/μL,direct correlations were identified between IL-2+IFN-γ+/IL-2+/IFN-γ+CD8 T cells and viral load or CD4 count.Conclusions Universal consistent inverse correlation was only indentified between CD4 count and viral load.The relationship between HIV-1 specific CD8 T cell responses and CD4 count/viral load varied in different CD4 strata,which showed that better preserved CD4 T cells were correlated with better CD8 T cell functions.     

Association between Nef-specific CD8 T-cell responses and disease progression in HIV-1 subtype B infection

Background The correlation between HIV-1 Nef-specific CD8 T-cell responses and markers of HIV-1 disease progression still remains unclear. This study analysed and compared the role of HIV-1 Nef-specific CD8 T-cell responses in patients with different disease status. Methods Two groups of patients with HIV-1 subtype B infection were selected according to CD4 count and clinical manifestations： long-term nonprogresssors （LTNPs, n = 20） and advanced progressors （APs, CD4 count 〈500 cells/pl, n = 34）. Nef-specific CD8 T-cell responses were studied by interferon- T ELISpot assay against 3 pools of HIV-Nef peptides. Results Nef-specific CD8 T-cell responses did not correlate with viral load or CD4 count in all patients and no significant differences were found in the magnitude of Nef-specific CD8 T-cell responses between groups LTNPs and APs （670 SFC/106 peripheral blood mononuclear cells vs 1107 SFC/106 peripheral blood mononuclear cells, P = 0.255）. Further comparisons showed that there were also no significant correlations observed in group LTNPs, but Nef-specific CD8 T cells correlated negatively with viral load （r = -0.397, P = 0.020） and positively with CD4 count （r = 0.364, P = 0.034） in group APs. Conclusion These data suggest that different correlation patterns between Nef-specific CD8 T-cell responses and disease progression exist in LTNPs and APs. Although a negative association was observed with concurrent plasma HIV RNA in APs, Nef-specific CD8 T-cell responses might fail to play a protective role in different stages of HIV- 1 infection.     

CD4+ T cell-mediated presentation of non-infectious HIV-1 virion antigens to HIV-specific CD8+ T cells

Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^＋ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^＋ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^＋ T cells. Cross presentation required the entry of HIV-1 to CD4^＋ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^＋ mediated activation of HIV-specific CD8^＋ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^＋ T cells cross presenting HIV-1 antigen to activate CD8^＋ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.     

中国部分地区HIV感染者/艾滋病患者外周血单核/巨噬细胞功能与疾病的进展关系

目的 通过对中国HIV感染者／艾滋病（AIDS）患者外周血单核／巨噬细胞标志抗原CD14及其早期活化分子CD69的研究,探讨其外周血单核／巨噬细胞的功能状态与HIV感染者疾病进程的关系。方法采集57例未经抗病毒治疗的HIV感染者／AIDS患者及32例健康人抗凝全血,运用流式细胞分析技术对CD4^＋T淋巴细胞、CD14^＋细胞及其CD69抗原表达情况进行测定,并采用实时荧光定量RT-PCR技术检测患者血浆HIV-1载量。结果（1）HIV感染者／AIDS患者外周血CD14^＋细胞颗粒度SSC值为76±16,CD69分子在CD14^＋细胞的表达率为27％±4％,均明显高于对照组（P〈0．05）,其中AIDS组高于HIV慢性感染（HIV）组及长期不进展（LTNP）组,HIV组高于LTNP组（P〈0．05）,LTNP组与对照组比较差异无统计学意义;外周血CD14^＋细胞比例、CD14抗原水平与对照组相比差异无统计学意义。（2）HIV感染者／AIDS患者外周血CD69分子在CD14^＋细胞的表达率与CD4^＋T淋巴细胞绝对值呈明显负相关（r=-0．872,P〈0．01）,与HIV-1RNA病毒载量呈显著正相关（r=0．697,P〈0．01）。结论中国部分地区HIV／AIDS患者外周血单核／巨噬细胞的活化和吞噬功能较健康对照组有显著上升,且与疾病进展密切相关。     

Association of IL-7 with disease progression in Chinese HIV-1 seropositive individuals

Background Elevated levels of interleukin-7 (IL-7) have been correlated with CD4(+) T cell depletion and the emergence of syncytium-inducing (SI) variants in human immunodeficiency virus type-1 (HIV-1) infection, and suggested as an indicator of acquired immunodeficiency syndrome (AIDS) disease progression. Therefore, we investigated the effects of IL-7 on disease progression and virus phenotype in Chinese HIV/AIDS patients. Methods In a cross-sectional study of 71 untreated HIV-1 seropositive individuals and 12 healthy donors, plasma IL-7 levels were determined by an ultra sensitive enzyme-linked immunosorbent assay (ELISA), and its relations to CD4(+) T cells, CD8(+) T cells, plasma viral loads and HIV phenotypes were analyzed. Results Significant higher IL-7 levels were found in Chinese HIV/AIDS patients [(3.33 ± 3.60) pg/ml] than those of health controls [(1.2 ± 0.81) pg/ml] ( P &lt;0.05), and IL-7 levels were inversely associated with CD4(+) T cell counts ( r = － 0.497, P &lt;0.01). Furthermore, IL-7 levels were significant higher in patients with SI variants [(9.12 ± 4.55) pg/ml] than those with non-syncytium-inducing variants [(1.50 ± 2.69) pg/ml] ( P &lt;0.01). Conclusions Increased IL-7 levels were found in Chinese HIV/AIDS patients and significantly associated with disease progression, thus increased IL-7 plasma levels may indicate disease progression.     

人类免疫缺陷病毒-1感染者外周血单个核细胞体外培养的免疫学及病毒学特点

目的观察人类免疫缺陷病毒(HIV)感染者外周血单个核细胞(PBMC)体外培养过程中免疫学及病毒学的动态变化特点,并评价培养的细胞体系抗病毒活性。方法采集14例HIV感染者和6名健康人的PBMC,体外经多种细胞因子诱导培养,每3天观察细胞增殖情况,同时检测细胞表型、上清中细胞因子浓度和病毒载量。结果培养的健康人PBMC在(35±5)d最大增殖(61±8)倍;7例培养成功的HIV感染者PBMC在(21±6)d最大增殖(17±13)倍,另7例HIV感染者PBMC培养失败;同时发现HIV感染者PBMC体外培养最大增殖时间与其培养前外周血基础CD4/CD8比值呈明显正相关(P<0.05)。表型分析发现,培养的PBMC为优先CD8细胞增殖的异质T细胞群,主要由CD4、CD8及CD3CD56细胞组成;部分HIV感染者PBMC培养期间分泌白细胞介素(IL)1α、IL12、肿瘤坏死因子(TNF)α和IL10等细胞因子能力较高;而11/12例HIV感染者PBMC体外培养初期可扩增出大量病毒,但随着培养时间的延长,病毒载量逐渐降低甚至低于检测限。结论体外大量扩增基础CD4/CD8比值较高的HIV感染者外周血PBMC是可行的,扩增的细胞具备较强的Th1细胞免疫反应能力,为进一步开展艾滋病的免疫细胞治疗提供必要的实验数据。     

HIV-specific T cell immunity across the entire HIV genome in Chinese men who have sex with men

Background Man who has sex with man （MSM） is one of the high risk groups for spreading HIV/AIDS. It was reported that the most prevalent human irnmunodeficiency virus type 1 （HIV-1） strain among MSM is subtype B; however, T cell immunity remains unknown across the HIV-1 B genome in this population. Methods Using Elispot assay with synthetic peptides spanning the sequence of HIV-1 consensus B, HIV-l-specific cytotoxic T-cell lymphocyte responses were quantified among 3 treated and 19 untreated HIV-1 infected MSM from Beijing, China. Cross-sectional association between viral loads and cellular immune responses were analyzed. Results Peptide pools corresponding to each HIV-1 protein were used for Env, Gag, Pol, Nef, Tat/Rev, Vpr/Vpu and Vif. The results showed that the magnitude of T cell responses in the 3 treated HIV^＋ MSM group [median, 770 spot forming cells （SFCs） per 106 peripheral blood mononuclear cells （PBMCs）] might be significantly lower than that in the 19 untreated HIV^＋ MSM group （median, 6175 SFCs per 106 PBMCs）. Nef, Gag and Pol are the most frequently targeted HIV-1 antigens; and 16 subjects （73%） were identified with vigorous T cell immunity against each of these three proteins. The overall magnitude of T cell immunity closely related to its breadth （r=-0.72, P〈0.05） and was inversely but weakly associated with viral loads （r=-0.15）. Further analysis showed that both Gag （r=-0.24） and Pol specific T cells （r=-0.12） contributed to this inverse association whereas Nef specific T cells showed no association with viral loads. Conclusions The magnitude of HIV-1 specific T cells is inversely but weakly associated with viral loads among MSM; HIV-specific T cell responses against conservative sequences （Gag and Pol） are the main contributors to this association among Chinese HIV^＋ MSM. These findings have important implications for vaccine design.     

Activation and coreceptor expression of T lymphocytes induced by highly active antiretroviral therapy in Chinese HIV/AIDS patients

Background At the end of 2005, 650 000 people lived with human immunodeficiency virus type-1 (HIV-1) in China, of whom 75 000 were AIDS patients. Many AIDS patients received highly active antiretroviral therapy (HAART) supported by the “China CARES” program but the immune responses of HAART were seldom reported. This study investigated the effect of HAART on the activation and coreceptor expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect on immune reconstitution. Methods Seventeen HIV/AIDS patients were enrolled and three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples taken from the patients before and after 3- or 6-month HAART.Results The activation percents of CD4(+), CD8(+) T lymphocytes were significantly higher before therapy than the normal controls (HLA-DR/CD4: 40.47±18.85 vs 11.54±4.10; CD38/CD4: 81.34±10.86 vs 53.34±11.44; HLA-DR/CD8: 63.94±12.71 vs 25.67±9.18; CD38/CD8: 86.56±11.41 vs 58.84±6.16, all P&lt;0.01). After 6-month combined antiretroviral treatment, the activation of T lymphocytes in HIV/AIDS patients was significantly decreased (HLA-DR/CD4: 28.31±13.48; CD38/CD4: 69.88±12.64; HLA-DR/CD8: 46.56±18.64; CD38/CD8: 70.17±14.54, all P&lt;0.01 compared with the pre-treatment values). Before the treatment, CCR5 expression on CD8(+) T lymphocytes was up-regulated while CXCR4 expression on CD8(+) T lymphocytes downregulated in HIV/AIDS patients compared with the normal controls (CD8/CCR5: 70.91±10.03 vs 52.70±7.68; CD8/CXCR4: 24.14±11.08 vs 50.05±11.68, all P&lt;0.01). After 6-month HAART, CCR5 expression on CD8(+) T lymphocytes significantly decreased (56.35±12.96, P&lt;0.01), while CXCR4 expression on CD8(+) T lymphocytes increased (36.95±9.96, P&lt;0.05) compared with the pre-treatment and the normal controls. A significant statistical relationship was observed between the expression of activation markers, CCR5 and the CD4(+) T lymphocyte counts after HAART (P&lt;0.05).Conclusions Reduced activation of T lymphocytes and a normalization of coreceptor expression were observed in Chinese HIV/AIDS patients after HAART. Immunity can be restored in HIV/AIDS patients receiving HAART.     

梅毒对HIV-1感染者病毒载量和CD4+T细胞计数的影响

目的:评估梅毒对HIV-1感染者血浆HIV-1病毒载量,CD4 T细胞计数的影响.方法:于1年前对HIV-1感染者进行梅毒ELISA和RPR检测,对RPR检测阳性者根据其CD4 T细胞计数和病毒载量进行配对,与1年后重新检测CD4 T细胞计数与病毒载量比较,用配对资料的t检验分析梅毒对HIV感染者CD4 T细胞与病毒载量的影响.结果:在271例HIV-1感染者中,共11例梅毒阳性者,占4.1%.本研究中包括HIV-1感染者20例,其中10例梅毒与HIV-1共感染者.在梅毒与HIV共感染者病例中,CD4 T细胞计数明显降低(99个细胞/ml),但病毒载量的变化没有显著差异.结论:梅毒显著地降低HIV-1感染者的CD4 T细胞数量,但病毒载量没有明显的变化.为了延缓HIV-1感染者进入AIDS阶段的时间,应加强对梅毒的治疗和采取相应的预防措施.