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。     

HIV/HCV合并感染者淋巴细胞活化及第二受体表达的研究

目的了解中国不同疾病进展阶段人类免疫缺陷病毒和丙型肝炎病毒（HIV／HCV）合并感染者T淋巴细胞与自然杀伤细胞（natural killer cells，NK）数量变化及T淋巴细胞活化、受体表达情况，并探讨HCV感染对HIV感染免疫指标及疾病进展的影响。方法应用流式细胞术分析228例不同疾病进展阶段的HIV／HCV合并感染者及101例单纯HIV感染者外周血T淋巴细胞、NK细胞数量及T淋巴细胞活化受体（HLA-DR、CD38）、第二受体（CCR5、CXCR4）表达情况。结果（1）HIV／HCV合并感染组中，CD4^＋T淋巴细胞、NK细胞数量随疾病进展持续下降，其中艾滋病组（AIDS）明显低于无症状HIV感染组（HIV）（P〈0．05），HIV组明显低于长期不进展组（LTNP）（P〈0．01），LTNP组与健康对照组差异无统计学意义。LTNP组、HIV组及AIDS组CD4^＋、CD8^＋T细胞表面活化受体HLA-DR、CD38的表达依次升高，其中各组间CD8／CD38的升高差异均有统计学意义（P〈0．05），AIDS组CD4／HLA-DR、CD8／HLA-DR的升高明显高于LTNP组和HIV组（P〈0．01）。LTNP组、HIV组及AIDS组CD4^＋、CD3^＋T细胞表面CCR5的表达亦依次升高，各组间差异均有统计学意义（P〈0．05）；CD3^＋T细胞表面CXCR4的表达依次升高，AIDS组明显高于HIV组和LTNP组（P〈0．01）。（2）HIV／HCV合并感染组与单纯HIV感染组相比，AIDS组NK细胞明显下降（P〈0．05），CD4^＋T细胞下降，但无统计学意义，CD4／HLA-DR、CD8／HLA-DR、CD4／CXCR4、CD3／CXCR4明显升高（P〈0．01）；HIV组NK细胞明显下降（P〈0．01），CD4／CXCR4明显升高（P〈0．05）；LTNP组各项指标与单纯HIV感染组相比差异无统计学意义。（3）HIV／HCV合并感染组的HIV病毒载量随疾病进展不断升高，与单纯HIV感染组相比差异无统计学意义；HCV病毒载量在疾病不同阶段差异无统计学意义（P〉0．05）。结论随疾病进展，HIV／HCV合并感染者的免疫功能逐渐下降，HIV病毒载量逐渐升高。与单纯HIV感染相比，合并HCV感染可通过破坏机体天然免疫功能、促进免疫系统活化和受体表达，加速HIV感染的疾病进展。     

中国HIV-1暴露未感染者及感染者趋化因子受体CX3CR1的表达研究

目的 通过分析中国HIV-1暴露未感者（exposed semnegative individuals，ESN）及HIV-1感染者外周血中CX3C1^＋CD8^＋／CD3^＋、CX3CR1^＋CD16^＋／CD3^-、CX3CR1^＋CD56^＋／CD3^-细胞百分率及绝对值的变化，探讨CX3CR1受体与HIV-1感染及疾病进展的关系。方法 采集19例ESN、34例未经治疗的HIV-1感染者及18例健康人抗凝静脉血，采用流式细胞仪检测技术，分析计算三色荧光抗体标记的全血中CX3CR1^＋CD8^＋／CD3^＋、CX3CR1^＋CD16^＋／CD3^-、CX3CR1^＋CD56^＋／CD3^-细胞百分率及绝对值。结果 ESNCX3CR1^＋CD8^＋／CD3^＋细胞的百分率是11．05％±6．52％，绝对值是81．16±13．67个／山，显著高于正常对照组（百分率是5．69％±3．94％，绝对值是37．36±8．28个/μl）；HIV-1感染组CX3CR1^＋CD8^＋／CD3^＋细胞的百分率是20．98％±11．88％，绝对值是166．38±138．38个/μl，显著高于正常对照组。ESN的CX3CR1^＋CD16^＋／CD3^-细胞的绝对值是312．49±159．45个／m，显著高于HIV-1感染组（108．83±119．35个／ta）。ESN的CX3CR1^＋CD56^＋／CD3^-细胞的绝对值是316．98±162．56个叫，显著高于HIV-1感染组（100．27±114．57个／ta）。HIV．1感染者的CX3CR1^＋CD16^＋／CD3^-、CX3CR1^＋CD56^＋／CD3^-细胞的绝对值与CIM^＋T淋巴细胞的绝对值呈明显正相关（P〈0．05）。结论CX3CR1^＋CD8^＋／CD3^＋细胞在中国ESN体内起保护作用，而在HIV-1感染者体内发挥有限的保护作用。表达CX3CR1受体的NK细胞可以作为监测HIV-1感染者免疫状况的一个指标。     

CD4+ CD25+调节性T细胞在HIV/AIDS患者中的作用及其与HIV病毒载量的相关性研究

目的 研究HIV感染者／AIDS患者外周血CD4^＋ CD25^＋ 调节性T细胞（CD4^＋ CD25^＋ regulatory Tcell，Treg）频率、功能及其临床意义。方法 选择31例HIV感染者／AIDS患者和30例健康对照者，采用流式细胞仪检测各组外周血Treg的表型和频率。采取MACS磁珠分选CD4^＋CD25^＋T细胞，利用[^3H]胸腺嘧啶掺入法检测CD4^＋ CD25^＋T细胞在特异性HIV抗原刺激下对CD4^＋ CD25-T细胞的增殖影响。结果HIV／AIDS患者组与正常对照组相比较，外周血CD4^＋ CD25^＋ T细胞频率在统计学上差异无统计学意义。与正常对照组比较，HIV感染者外周血CD4^＋ CD25^＋ T细胞频率升高，差异有统计学意义（P〈0.01）；与正常对照组比较，AIDS患者者外周血CD4^＋ CD25^＋ T细胞频率降低，差异有统计学意义（P〈0．0001）。HIV RNA病毒载量与患者外周血CD4^＋ CD25^＋ T细胞数量呈正相关性（P〈0．01）。CD4^＋ CD25^＋ T细胞具有抑制HIV特异性的CD4^＋ CD25^- T细胞的增殖作用。结论HIV感染者／AIDS患者的细胞免疫功能紊乱，CD4^＋ CD25^＋ T细胞能抑制HIV感染者／AIDS患者的HIV特异性细胞免疫反应，促进HIV病毒复制，与形成持续HIV感染有关。     

趋化因子及受体与中国HCV/HIV合并感染相关性的研究

目的：探讨趋化因子自细胞介素8（IL-8）、干扰素诱导蛋白10（IFN-inducible 10-kdaprotein，IP-10）及趋化因子受体CCR5、CXCR3，在丙肝病毒（HCV）单纯感染，艾滋病病毒（HIV）单纯感染和HCV／HIV合并感染过程中的表达及意义。方法：采用流式细胞术，检测HCV感染组（n=21）、HIV感染组（n=14）、HCV／HIV感染组（n=28）及正常对照组（n=30）人外周血CD4^＋T淋巴细胞和CD8^＋T淋巴细胞表面CCR5、CXCR3的表达。ELISA方法检测血清趋化因子IL-8、IP-10含量。结果：HCV感染组、HIV感染组和HCV／HIV合并感染组，血清IP-10水平都明显升高，而在合并感染组水平最高；血清IL-8水平在3组亦明显升高。HIV感染组及HCV／HIV合并感染组CD4^＋T细胞表面CXCR3表达显著降低（P〈0．001），CD8^＋T细胞表面CXCR3表达显著升高（P〈0．001）；HCV感染组CD4^＋及CD8^＋T细胞表面CXCR3表达轻度升高，但差异不显著。HCV感染组及HCV／HIV合并感染组CD4^＋及CD8^＋T细胞表面CCR5表达显著降低（P〈0.001）；HIV感染组CD4^＋及CD8^＋T细胞表面CCR5表达显著升高（P〈0.001）。结论：中国HCV／HIV合并感染患者中，血清IL-8和IP-10水平都明显升高；受体CXCR3在CD4^＋T细胞表面表达降低，而在CD8^＋T细胞表面表达升高；受体CCR5在CD4^＋及CD8^＋T细胞表面表达降低，提示趋化因子及受体与HCV／HIV合并感染密切相关。     

休克期大面积切痂对严重烧伤大鼠细胞免疫功能影响的研究

目的 观察休克期大面积切痂对严重烧伤大鼠细胞免疫功能的影响，探索改善烧伤后机体免疫功能紊乱的有效方法。方法 将大鼠分成休克期切痂组（A组）、常规切痂组（B组）和正常对照组（C组）。A、B组造成30％TBSAⅢ度烫伤，C组不烫伤。A组伤后第6h、B组伤后第4d切痂，并于伤后第1、5、9d各活杀10只，取材送检，观察其免疫指标的变化。结果 （1）A、B组与C组比较：A、B组烫伤大鼠各时相点CD3^＋T细胞变化不大（P〉0．05），但CD4^＋T细胞、CD4^＋／CD8^＋比值明显下降、CD8^＋T细胞增高（P〈0．05或P〈0．01）。NK细胞活性明显下降（P〈0．05或P〈0.01），外周血CD25^＋T淋巴细胞表达及经活化后脾脏CD25^＋T淋巴细胞表达明显下降（P〈0．05或P〈0．01）。（2）A组与B组比较：A组CD4^＋T细胞、CD4^＋／CD8^＋比值明显升高、CD8^＋T细胞降低（P〈0．05或P〈0．01），NK细胞活性明显升高（P〈0．05或P〈0．01），外周血CD25^＋T淋巴细胞表达及经活化后脾脏CD25^＋T淋巴细胞表达均明显升高（P〈0．05或P〈0．01）。结论 （1）大鼠烫伤后细胞免疫状况发生了明显变化。（2）休克期切痂可以改善烫伤大鼠T淋巴细胞亚群分布，提高NK细胞活性，增加外周血CD25^＋T淋巴细胞的表达。提高经活化后脾脏CD25^＋T淋巴细胞数。从而改善烫伤大鼠伤后机体的细胞免疫功能。     

CD4+ CD25+调节性T细胞对树突状细胞的杀伤作用

目的 探讨CD4^＋CD25^＋调节性T细胞是否对树突状细胞发挥免疫调节作用及其可能的机制。方法 用MACS（magnetic cell sorting）从BALB／c小鼠静息T细胞分离纯化CD4^＋CD25^＋T细胞，体外细胞增殖实验观察其对CD4^＋CD25^＋T细胞的免疫抑制作用；GM-CSF／IL-4培养自体小鼠骨髓来源DC，FACS（fluorescence-activated cell sorting）鉴定其表面分子特性；以CD3／CD28单克隆抗体活化CD4^＋CD25^＋调节性T细胞，FACS体外杀伤实验研究其对自体DC的调节作用，并观察穿孔素抑制剂EGTA对上述作用的影响。结果 用MACS法成功分离出CD4^＋CD25^＋T细胞，纯度可达98％，特异性表达而Faxp3基因，能明显抑制CD4^＋CD25^＋T细胞的体外增殖；骨髓来源的DC表达CDllc、MHCⅡ及少量协同刺激分子CD80、CD86；FACS体外杀伤实验证实以CD3／CD28抗体体外活化的CD4^＋CD25^＋调节性T细胞对自体DC有显著杀伤作用（P〈0．05），穿孔素抑制剂EGTA能部分抑制该杀伤效应（P〈0．05）。结论 CD4^＋CD25^＋调节性T细胞可通过杀伤作用对自体DC发挥免疫调节作用，穿孔素／颗粒酶杀伤途径可能参与其中。     

IL-7对中国HIV/AIDS患者病程的影响

目的 了解IL-7对中国HIV／AIDS患者病程的影响。方法应用超敏感酶免法对66例中国HIV／AIDS感染者及8例健康对照者血浆IL-7水平进行定量检测，分析其与CD^＋T细胞绝对值、血浆病毒载量及HIV表型的相关性；并且在体外研究rhIL-7对人PBMC中T淋巴细胞增殖及CXCR4表达的影响。结果中国HIV／AIDS患者血浆IL-7水平高于健康对照（P〈0．05），与CD4^＋T细胞绝对值负相关（P〈0．01），与血浆病毒载量正相关（P〈0．05）。rhIL-7可在体外促进T淋巴细胞增殖反应及CXCR4表达。结论中国HIV／AIDS患者血浆IL-7水平升高，且与疾病进展密切相关，可作为疾病进展的相关标志之一。     

慢性肝脏疾病中CD3^-CD161^＋NK和CD3^＋CD161^＋NKT细胞亚群的变化研究

目的探讨CD3^-CD161^＋NK、CD3^＋CD161^＋NKT细胞在慢性肝炎／肝硬化及肝细胞癌患者肝脏组织及外周血中表达及意义。方法利用流式细胞仪对31例肝细胞癌患者、59例慢性肝炎／肝硬化患者肝脏组织及外周血、15例正常肝脏组织、48例正常人外周血中的CD3^-CD161^＋NK和CD3^＋CD161^＋NKT进行定量分析。结果慢性肝炎／肝硬化组CD3^-CD161^＋NK细胞[（13．4±1．3）％]和肝细胞癌癌周组CD3^-CD161^＋NK细胞[（16．7±4．8）％]及远离肝癌组的肝脏组织CD3^-CD161^＋NK细胞[（22．0±4．4）％]与正常肝脏组织CD3^＋CD161^＋NK细胞[（35．1±7．2）％]相比,肝细胞癌癌周肝脏组织内含量最低（t值分别为2．301、2．137、2．034,P〈0．05）;外周血中肝细胞癌组CD3^-CD161^＋NK细胞f（11．6±6．3％）]、CD3^＋CD161^＋NKT细胞[（14．7±6．2）％]与慢性肝炎／肝硬化组CD3^-CD161^＋NK细胞[（10．8±1．7）％]、CD3^＋CD161^＋NKT细胞[（12．5±0．8）％]、正常对照组CD3^＋CD161^＋NK细胞[（7．5±0．8）％]、CD3^-CD161^＋NKT细胞[（13．8±1．7）％]相比肝癌组CD3^-CD161^＋NKT细胞含量最高（t值分别为2．134,2．099,P〈0．05）,肝癌组CD3^＋CD161^＋NKT细胞含量最高（t值分别为2．125,2．154,P〈0．05）。结论由于NK细胞及NKT细胞数量减少或／和活性降低,使肿瘤细胞逃逸了免疫监视,可能促进了肿瘤的发生、发展及转移。     

慢性乙型肝炎患者抗病毒治疗前后外周血树突状细胞和淋巴细胞亚群的变化及意义

目的 分析慢性乙型肝炎患者拉米夫定抗病毒治疗前后外周血树突状细胞和淋巴细胞亚群变化。方法 对16例拉米夫定抗病毒治疗有效的慢性乙型肝炎患者动态观察48周，在治疗前、后对外周血单核细胞来源的树突状细胞进行体外培养，用流式细胞仪检测DC表面分子及淋巴细胞亚群水平，观察治疗前、后的变化。结果 16例患者中，11例治疗持续有效，未发生YMDD变异，5例发生变异。无变异组的慢性乙肝患者，治疗12周时，HLA—DR水平较治疗前降低（P〈0．05）；治疗48周时，CD80、CD40和CD1a与治疗前比明显提高（P〈0．05）而HLA—DR恢复至治疗前水平。变异组患者。治疗12周时，CD83及HLA—DR降低（P〈0．05）；治疗48周时，HLA-DR仍低于治疗前（P〈0．05）。无变异组患者，治疗12周时，CD4^＋T细胞、CD8^＋T细胞、NK细胞、CD19^＋B细胞和CD4^＋／CD8^＋T细胞比值均无明显变化；48周时，CD4^＋T细胞比例增高，NK细胞比例下降（P〈0．05）。而变异组患者的淋巴细胞亚群则无显著改变。结论 拉米夫定治疗持续有效组，DC表面共刺激分子CD80、CD40可随着HBV被长时间有效抑制而得到部分恢复，治疗过程中有DC表面的HLA-DR暂时降低，而后HLA—DR水平恢复和CD1a明显提高，同时外周血CD4^＋T细胞比例上升和NK细胞比例下降。而发生YMDD变异组。DC表面HLA—DR呈现持续性降低。     

Differential Expression of Perforin in Cytotoxic Lymphocyte in HIV/AIDS Patients of China

Cytotoxic lymphocytes are critical in the control of HIV replication, it has been shown that perforin is the key effector of killing machinery for CTLs and NK cells, so we investigated the circulating levels of perforin in CD8⁺T cells and NK cells by flow cytometry intracellular stain in Chinese HIV infected individuals, its association with disease progression was analyzed. Our results showed that NK cells express perforin more efficiently than CD8⁺T cells, CD8⁺T cells expressed perforin higher than that of healthy controls, but NK cells expressed lower perforin than that of healthy controls, both were not correlated with disease progression. but significantly associated with their numbers, anti-retrovirus therapy had no evident effects on peforin expression in CD8⁺T cells, but enhanced perfrin expression in NK cells, perforin expression in CD8⁺T cells and CD16⁺NK cells correlate with CD4⁺T cell counts significantly in HAART-treated group. Therefore, different mechanisms may be involved in regulating peripheral perforin expression in different cell types.     

Altered Coexpression of Lectin-Like Receptors CD94 and CD161 on NK and T Cells in HIV Patients

HIV patients either on highly active antiviral therapy (HAART) or therapy naive were analyzed for their CD56 phenotype and cytokine production in comparison to healthy controls (HC). Both NK cell populations (CD56(dim) and CD56(bright)) are found to be present in all groups with selectively decreased CD56(dim) NK cells in HAART naive patients. Patients on HAART exhibited significantly diminished numbers of CD161+CD56(dim) NK cells. CD56(dim) were equally potent in producing IFNgamma in all three groups. The number of TNFalpha+CD56(bright) NK cells from patients on HAART and TNFalpha+CD56(dim) NK cells from HAART naive patients was significantly reduced as compared to healthy controls. In summary our data revealed that functional capacities and coexpression patterns of lectin-like receptors on lymphocytes are differentially affected in HIV patients depending on the state of therapy (under HAART or HAART naive) or the cell type (NK or T cells), respectively.     

高效抗逆转录病毒治疗对中国HIV/AIDS患者淋巴细胞活化及第二受体表达的影响

目的　了解高效抗逆转录病毒治疗后中国HIV/ AIDS患者淋巴细胞活化及CCR5、CXCR4表达的变化,探讨HIV感染者对于抗病毒治疗的免疫应答。方法　10例HIV /AIDS患者给予高效抗逆转录病毒治疗(HAART),用流式细胞仪检测治疗前和治疗第3、6 个月T淋巴细胞活化(HLA DR、CD38表达)及第二受体CCR5、CXCR4表达情况,比较HIV/ AIDS患者治疗前后淋巴细胞活化、第二受体表达的变化。结果　治疗前,10例HIV /AIDS患者CD4+、CD8+ T淋巴细胞活化水平均明显高于健康对照,CD8+ T淋巴细胞表面CCR5的表达明显高于健康对照,CXCR4 的表达明显低于健康对照(P<0.05);HAART治疗后,患者淋巴细胞活化水平随治疗时间明显下降(P<0.05),CD8+ T淋巴细胞表面CCR5表达水平显著降低(P< 0. 01), CXCR4 的表达升高;治疗6 个月时, CD38 CD4、HLA DRCD38 CD4、CCR5 CD8、CXCR4 CD8表达水平恢复至健康人水平;HIV AIDS淋巴细胞活化水平及第二受体CCR5的表达降低与HAART治疗后CD4+T淋巴细胞数量的升高具有显著的相关性。结论HAART能够降低中国HIV /AIDS患者淋巴细胞活化水平,使第二受体表达水平趋于正常,促进免疫功能的恢复。     

Expression of perforin on HIV-1-specific CD8+ lymphocytes after immunization with a gp120-depleted, whole-killed HIV-1 immunogen.

We examined HIV-1 antigen specific intracellular expression of perforin on CD4+ and CD8+ lymphocytes in subjects with chronic HIV-1 infection on antiviral drug therapy after immunization with a gp120-depleted, whole killed HIV-1 immunogen (inactivated, gp120-depleted HIV-1 in IFA, REMUNE). Based upon previous results, we hypothesized that the restoration of adequate T helper immune responses by vaccination against HIV-1 could result in the augmentation of CD8+ lymphocyte immune responses measured as perforin expression. In the current study we observed an increase in the frequency of perforin in CD8+ lymphocytes in HIV infected individuals immunized with a gp120-depleted HIV-1 immunogen while on antiviral drug therapy. Furthermore, the frequency of HIV-specific CD8+ perforin expressing cells correlated with the T helper immune response as measured by the lymphocyte proliferative response (LPR). The induction of such responses with immunization may have direct antiviral consequences and is being studied in ongoing clinical trials.     

Alterations of Natural Killer Cell and T-Lymphocyte Counts in Adults Infected with Human Immunodeficiency Virus through Blood and Plasma Sold in the Past in China and in Whom Infection Has Progressed Slowly over a Long Period

Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)-positive individuals infected through the past sale of blood and plasma without receiving antiretroviral therapy in the People’s Republic of China. According to CD4 T-cell counts these HIV-infected adults were stratified into three groups: long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell counts in long-term slow progressors were higher compared to HIV infection and AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05), whereas NKT cell counts in slow progressors and the HIV infection group were not different from those of normal controls. NK cell counts in HIV-seropositive subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P < 0.05). The CD8 T-cell counts were higher in slow progressors compared to those with HIV infection, AIDS patients, and normal controls. These results indicated that HIV infection causes alterations of NK cells and T cells in slow progressors, HIV-infected subjects, and AIDS patient groups, but no difference was found in NKT cell counts and percentages in slow progressors and the HIV-infected group compared to normal controls.     

中国HIV/AIDS患者NK细胞及NKT细胞变化的检测

目的　探讨HIV感染后机体NK(naturalkillercells)及NKT细胞的变化情况。方法　取外周血细胞 ,用标记荧光的抗体进行染色 ,流式细胞仪分析HIV AIDS患者NK和NKT细胞的变化。结果　HIV AIDS患者NK、NKT细胞和CD4 + T细胞显著低于正常对照 ;CD8+ T细胞显著高于正常对照。HIV AIDS患者NK百分数显著低于正常对照 ,与CD4 + T细胞数量成正比 ,r=0 .2 89,P <0 .0 1 ;NKT细胞数量与CD4 + T细胞数量成正比 ,r =0 .378,P <0 .0 1 ;与CD8+ T细胞数量成正比 ,r =0 .340 ,P <0 .0 1 ;长期不进展组NKT、NK细胞数量与正常对照组差异无显著性。结论　HIV感染可明显降低HIV AIDS患者NK和NKT细胞数量 ,NK和NKT细胞变化与疾病进展密切相关。     

Reduction of viral load and immune complex load on CD4+ lymphocytes as a consequence of highly active antiretroviral treatment (HAART) in HIV-infected hemophilia patients.

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV)-induced immune complex load on circulating CD4+ blood lymphocytes is associated with dysfunction and depletion of CD4+ lymphocytes and with increased monocyte/macrophage function. It was investigated whether HAART reduces both the viral load in plasma and the number of immune complex-coated CD4+ lymphocytes in the blood, and whether CD4+ counts are associated with viral load and/or immune complex load. MATERIALS AND METHODS: Twelve HIV+ hemophilia patients before and after conversion to HAART (group 1); eight HIV+ hemophilia patients without antiretroviral therapy (group 2). HIV-1 RNA copies in plasma using NASBA/Nuclisens kits; CD4+ lymphocytes coated in-vivo with immune complexes using flowcytometry on whole blood samples; in-vitro responses of immune complex-coated T lymphocytes in cell culture assays. RESULTS: After conversion to HAART there was a significant reduction of viral load, CD4+ gp120+, CD4+ IgM+, and CD4+ IgG+ circulating blood lymphocytes and plasma neopterin, paralleled by a significant increase of CD4+ and CD8+ counts. The percentage of immune complex-coated CD4+ lymphocytes of converted patients was significantly associated with CD4+ counts, in-vitro responses to concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), anti-CD3 and pooled allogeneic stimulator cells, and with plasma neopterin levels. CONCLUSION: HAART reduces viral load and HIV-induced immune complex load on circulating CD4+ blood lymphocytes. The results of this study can be interpreted to suggest that HAART increases CD4+ lymphocyte counts in part by counteracting HIV-induced autoimmune phenomena.     

Expression of perforin and cytolytic potential of human peripheral blood lymphocyte subpopulations.

To verify the physiological role of the pore-forming protein perforin in vivo, its expression in subpopulations of human peripheral blood lymphocytes was examined by immunocytochemical staining and their cytolytic potentials compared. In addition to NK cells and gamma delta T cells, which uniformly expressed abundant perforin in their cytoplasmic granules, only a small subpopulation of CD8+ alpha beta T cells contained perforin, namely the CD11b+ subset. However, in vitro activation with an anti-CD3 antibody and IL-2 induced perforin expression in approximately 50% of the CD8+CD11b- T cells and also in a small subset of CD4+ T cells. A distribution of perforin in CD8+ and CD4+ T cells, similar to in vitro activated T cells, was observed in fresh peripheral blood lymphocytes from infectious mononucleosis patients. In all instances, the expression of perforin correlated with the cytolytic potential of these subpopulations. The results strongly suggest that perforin plays a role in the manifestation of cytotoxic activity in vivo.     

Alterations of natural killer cell and T-lymphocyte counts in adults infected with human immunodeficiency virus through blood and plasma sold in the past in China and in whom infection has progressed slowly over a long period

Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)-positive individuals infected through the past sale of blood and plasma without receiving antiretroviral therapy in the People's Republic of China. According to CD4 T-cell counts these HIV-infected adults were stratified into three groups: long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell counts in long-term slow progressors were higher compared to HIV infection and AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05), whereas NKT cell counts in slow progressors and the HIV infection group were not different from those of normal controls. NK cell counts in HIV-seropositive subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P < 0.05). The CD8 T-cell counts were higher in slow progressors compared to those with HIV infection, AIDS patients, and normal controls. These results indicated that HIV infection causes alterations of NK cells and T cells in slow progressors, HIV-infected subjects, and AIDS patient groups, but no difference was found in NKT cell counts and percentages in slow progressors and the HIV-infected group compared to normal controls.