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.     

中国经采供血HIV感染长期不进展者CD4~+T淋巴细胞趋化因子受体表达研究

目的:了解中国经采供血HIV感染长期不进展者CD4+T淋巴细胞趋化因子受体表达,分析其与疾病不进展的关系。方法:收集43例经采供血HIV感染长期不进展者、82例无症状HIV感染者、35例AIDS病人及40例健康对照的抗凝全血,用流式细胞仪检测趋化因子受体CCR5、CXCR4的表达,并分析其与病毒载量、CD4+T淋巴细胞绝对值及T淋巴细胞活化的相关性。结果:长期不进展组CD4+T细胞表面CCR5的表达明显低于无症状HIV感染组及AIDS组(P0.01),与健康对照无显著差异;CD4+T细胞表面CXCR4的表达各组无显著差异。CD4+T细胞表面CCR5的表达与CD4+T细胞数量显著负相关(r=-0.498,P0.05),与病毒载量无显著相关性。CD4+T细胞表面CCR5的表达与HLA、CD38在CD4+、CD8+T细胞的表达水平显著正相关(P0.001,CD38在CD4+T细胞的表达除外),CD4+T细胞表面CXCR4的表达与HLA在CD4、CD8+T细胞的表达水平显著负相关(P0.01)。结论:HIV感染长期不进展者CD4+T细胞趋化因子受体CCR5表达维持较低水平,与疾病不进展相关。     

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。     

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-1感染者CD4+CD25+Foxp3+调节性T细胞与疾病进展相关性研究

目的对中国HIV-1感染者CD4~ CD25~ Foxp3~ 调节性T细胞水平及与疾病进展相关性进行研究,探讨CD4~ CD25~ Foxp3~ 调节性T细胞在HIV-1疾病进程中发挥的作用。方法选取35名HIV-1感染者及14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CD~ CD25~ Foxp3~ 调节性T细胞表达及淋巴细胞活化、凋亡水平。结果中国HIV-1感染者CD4~ CD25~ Foxp3~ T细胞水平与CD4~ T细胞显著负相关(r=-0.544,P=0.001),与病毒载量明显正相关(r=0.484,P= 0.026),与CD4~ T细胞凋亡(CD95表达)水平明显正相关(r=0.431,P=0.011)。艾滋病人CD4~ CD25~ Foxp3~ T细胞水平明显高于无症状HIV感染者(P<0.05),与健康人相比差异无统计学意义。艾滋病人CD4~ 、CD8~ T细胞凋亡水平明显高于无症状HIV感染者及健康人(P<0.05),艾滋病人及无症状HIV感染者CD4~ 、CD8~ T细胞活化明显高于健康人(P<0.05)。结论中国HIV-1感染者CD4~ CD25~ Foxp3~ 调节性T细胞水平与疾病进展明显相关。     

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感染者外周血CD4+ CD25+ Foxp3+/CD127low/-调节性T细胞表达水平对疾病进展的影响

目的:探讨HIV感染者外周血中CD4+ CD25+Foxp3+调节性T细胞(Treg)、CD4+ CD25+ CD127low/-Treg的水平及其与其他免疫指标的关系.方法:采集68例未经抗HIV治疗的HIV/AIDS患者(长期不进展组即LTNP组29例、典型进展的HIV感染组27例、AIDS组12例)及20例健康成人的外周抗凝全血,经免疫荧光染色,应用流式细胞仪分析CD4+T细胞、CD8+T细胞、NK细胞及CD4+CD25+Foxp3+/CD127low/-Treg的含量,并进行统计学分析.结果:除CD8+T细胞外,HIV/AIDS患者外周血中CD4+T细胞、NK细胞、CD4 +/CD8+结果均明显低于健康对照组(P＜0.05);随着疾病的进展,LTNP组、HIV组、AIDS组CD4+T细胞百分比、绝对值计数,CD8+T细胞绝对计数,NK细胞绝对计数,CD4 +/CD8+比值逐渐下降,而CD8+T细胞百分比逐渐上升.对CD4+ CD25+ Foxp3+ Treg与CD4+ CD25+CD127low/-Treg百分含量、绝对计数进行多重比较发现,各组间CD4+ CD25+ Foxp3+ Treg与CD4-CD25+ CD127low/-Treg所占CD4+T细胞百分含量的差异均有统计学意义(P＜0.05),并且随着疾病的发展,CD4+ CD25+ Foxp3+/CD127low/ Treg细胞百分含量逐渐上升,LTNP组与健康对照组之间、HIV组和AIDS组之间CD4+ CD25+Foxp3+/CD127low/ Treg绝对计数差异无统计学意义(P＞0.05),其余各组间的差异均有统计学意义(P＜0.05),并且随着疾病的发展,CD4+ CD25+ Foxp3-/CD127low/-Treg绝对计数逐渐下降.结论:CD4+ CD25+ Foxp3 +/CD127low/-Treg在HIV持续感染的免疫发病机制中有一定作用.     

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。     

HIV感染后CD8~+T细胞表面NK相关受体表达的变化

目的深入了解人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染后CD8+T细胞表面NK相关受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV感染者、11例AIDS患者、15例进行高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)者和13例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血CD8+T细胞表面NKG2D、NKG2A和KIR3DL1的表达。结果 HIV感染后CD8+T细胞表面NKG2D表达的百分比显著低于健康对照,NKG2D+NKG2A-表达的百分比随疾病进展逐渐下降,且NKG2D+NKG2A-表达的百分比与CD4+T细胞的绝对数量呈正相关。AIDS患者CD8+T细胞表达NKG2A显著高于其它各组,随着疾病的进展CD8+T细胞表达NKG2A+NKG2D-百分比逐渐上升,AIDS患者显著高于其它各组,经抗逆转录病毒治疗后下降至健康对照的水平,且NKG2A+NKG2D-表达的百分比与CD4+T细胞的绝对数量呈负相关。HIV感染后CD8+T细胞KIR3DL1+表达的百分比较健康对照并无显著差异。结论 HIV感染机体后,CD8+T细胞NK相关受体表达变化与疾病进展相关,抗病毒治疗后可恢复其变化。     

γδT、CD4 +CD25 +T细胞在HIV感染者/AIDS患者外周血的表达及其相关性研究

目的:了解γδT细胞、CD4 +CD25 +调节性T细胞(Treg)在HIV感染者/AIDS患者外周血中的表达水平,探讨γδT细胞、CD4 +CD25 + Treg在HIV感染/AIDS病情进展中的相关性以及可能的作用机制。 方法:采用免疫荧光单克隆抗体标记技术...     

Loss of mucosal CD4 lymphocytes is an early feature of HIV infection.

T cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluorescence using MoAbs to CD3, CD4, CD8, CD68, CD45RA, CD45RO and gp120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CD8 lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CD8+ lymphocytes. Although mucosal CD4,CD45RO+ 'memory' cells were decreased, CD8,CD45RO+ 'memory' cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.     

Selective increase of activation antigens HLA-DR and CD38 on CD4+ CD45RO+ T lymphocytes during HIV-1 infection.

Infection with HIV results in a progressive depletion of CD4+ T cells and leads to significant in vivo lymphocyte phenotype changes. In this regard, the expression of HLA-DR and CD38 on CD8+ T cells has been shown to increase dramatically with disease progression. We investigated the expression of both activation markers on CD4+ T cells in HIV-1-infected subjects at different clinical stages of infection and compared the in vivo activation of CD4+ T cells with parameters of viral activity and CD8+ T cell activation. Fresh peripheral venous blood was obtained from 54 HIV-infected subjects and from 28 uninfected healthy controls. Three-colour immunophenotyping of the CD4+ T cell subset showed that the proportion of CD4+ T cells expressing HLA-DR (10% in HIV-negative controls) or CD38 (62% in HIV-negative controls) was higher in asymptomatic (P < 0.05 for CD38) and symptomatic (P < 0.001 for HLA-DR and CD38) HIV-infected subjects than in controls, whereas the proportion of CD4+ T cells expressing CD45RO (54% in controls) remained relatively unchanged. Simultaneous expression of HLA-DR and CD38 on CD4+ T cells increased from 2.3% in controls to 11% (P < 0.001) in asymptomatic and 22% (P < 0.001) in symptomatic HIV-infected subjects. This relative increase of CD38 and HLA-DR expression occurred mainly on CD4+ T cells co-expressing CD45RO. Changes in expression of HLA-DR and CD38 on CD4+ T cells correlated with similar changes on CD8+ T lymphocytes, with the presence of HIV antigen in the circulation, and with the disease stage of HIV infection.     

CD80 and CD86 costimulatory molecules on circulating T cells of HIV infected individuals

The expression of CD80 and CD86 costimulatory molecules, typical for antigen presenting cells (APC), was measured on circulating T cells of 20 HIV-infected individuals and of 11 HIV-negative healthy controls. The CD80 and CD86 molecules were present on both circulating T subsets of HIV-infected individuals (mean of CD80 expression within CD4+ T cells [CD80/CD4]: 5.0%; and CD86/CD4: 2.6%; CD80/CD8 4.1% and CD86/CD8: 2.7%) and were associated with HLA-DR expression. Some CD80 and CD86 expression was also found in normal controls, and only the expression of CD86 was significantly (P < 0.05) increased on CD4 + and CD8 + T cells of HIV-infected individuals. The expression of CD28 was decreased on T cells of HIV-infected individuals and was negatively correlated to the expression of HLA-DR and CD86 (mean CD28 within CD3+T cells: HIV+ 29.5%, HIV - 67.6%; correlation coefficient, - 0.75 and - 0.71, respectively). The more the disease proceeds, the less CD28 and the more DR and CD86 are found on circulating T cells. This suggests that during HIV infection T cells themselves develop an antigen presenting phenotype by upregulating expression of HLA-DR, CD86 and CD80 molecules.     

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.     

Interferon-gamma and tumour necrosis factor-alpha production by CD4+ T and CD8+ T lymphocytes in AIDS patients with tuberculosis

Tuberculosis (TB) is usually more severe in HIV-infected patients, and the immune derangement found in co-infected patients may differ from that in each isolated disease. Following mitogen stimulation of peripheral blood mononuclear cells (PBMC), interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha production was evaluated in T cells by flow cytometry, and in culture supernatants by enzyme-linked immunosorbent assay (ELISA) in 33 individuals: 11 AIDS patients with tuberculosis, six asymptomatic HIV-1-infected patients, eight patients with tuberculosis and eight healthy controls. The proportion of CD4+ T lymphocytes expressing IFN-gamma did not differ between the groups, whereas a trend towards increased proportions of TNF-alpha-expression in CD4+ T cells was observed in the TB compared to the HIV group, while intermediate values were observed in co-infected patients. Detection of IFN-gamma and TNF-alpha in CD8+ T lymphocytes was higher in TB than in HIV individuals. Co-infected patients presented intermediate values for IFN-gamma, while TNF-alpha detection was similar to that in HIV mono-infection. In conclusion, the proportion of T cells expressing IFN-gamma was relatively preserved in co-infected patients compared to TB patients, while the percentage of T cells expressing TNF-alpha was decreased, mainly in CD8+ T lymphocytes. However, the marked reduction in T lymphocyte numbers in co-infected patients led to a striking reduction of both cytokines in PBMC supernatants, a finding that is consistent with the impaired response to Mycobacterium tuberculosis.     

HIV/AIDS患者疾病进程与CD4+CD25hi调节性T细胞之间相关性研究

目的 通过分析不同阶段HIV感染者外周血CD4+CD25hi调节性T细胞(CD4+CD25hiregulatory T cells,Treg cells)与外周血免疫状态和病毒载量的相关性,探讨Treg细胞对HIV/AIDS发病进程的影响.方法 采集116例HIV感染者和21例正常人对照外周血,用4色流式细胞术进行CD4+和CD8+T细胞绝对数计数;用3色流式细胞术进行Treg细胞测定;用荧光定量PCR法进行HIVRNA载晕测定.实验数据用回归统计学方法和T检验方法进行分析.结果 HIV感染者外周血Treg细胞频率在HIV感染初期显著下降,之后随着疾病的进程逐渐升高.在CD4+T细胞大于300/μl的患者低于正常对照组,在CD4+T细胞小于100/μl的患者高于正常对照组,差异具有统计学意义.Treg细胞频率与CD4+T淋巴细胞绝对数和CD4+/CD8+之间均呈负相关.其相关系数r和P值各为r=-0.564,P＜0.001和r=-0.377,P＜0.001;Treg细胞频率与血浆HIV病毒载量呈正相关,其相关系数r=0.514.P＜0.001.结论 CD4+CD25hi Treg细胞可能是参与艾滋病免疫发病机理的重要细胞,在HIV感染发病进程的不同阶段具有不同的意义,其确切机制有待进行进一步研究.     

Comparison of activation marker and TCR V beta gene product expression by CD4+ and CD8+ T cells in peripheral blood and lymph nodes from HIV-infected patients.

Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) V beta gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti-CD38, anti-HLA-DR and 13 anti-V beta MoAbs that cover, approximately, 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the V beta repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of V beta families expressed by CD4+ or CD8+ T cells had different repartition in LN and PB, whereas in each HIV+ patient, more V beta families exhibited different distributions and these differences recurred among certain V beta segments, such as V beta 5.3 and V beta 21 in the CD4+ T cell population and V beta 5.2/5.3, V beta 12 and V beta 21 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities.     

Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population

The proportion of human peripheral blood CD8+ T cells that are CD57+ CD28- is low at birth but increases with age and in individuals infected with human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV). These CD57+ CD28- CD8+ T cells contain large oligoclonal T-cell expansions whose antigen specificity is unknown. We identified clonal expansions of virus-specific memory cytotoxic T-lymphocyte precursors (CTLp) in both healthy carriers of HCMV and in asymptomatic HIV-infected subjects. In each subject, from the T-cell receptor (TCR) beta-chain hypervariable sequence of each immunodominant CTL clone, we designed complementary oligonucleotide probes to quantify the size and phenotypic segregation of individual virus-specific CTL clones in highly purified populations of peripheral blood CD8+ T cells. We found large clonal expansions of virus-specific CTL clonotypes in CD57+ CD28- CD8+ T cells. Using limiting dilution analysis, we found functional peptide-specific CTLp at high frequency in CD57+ CD28- cells. Thus, memory CTL specific for persistent viruses account for many oligoclonal expansions within CD57+ CD28- CD8+ T cells.     

Expression of CD28 on CD8+ and CD4+ Lymphocytes During HIV Infection

CD28 interaction with B7 molecules, expressed on the membranes of antigen-presenting cells, costimulates cytokine production, T-cell proliferation and generation of cytotoxic lymphocytes. The expression of CD28 markers on CD4⁺ and CD8⁺ lymphocytes was studied in a group of subjects at various stages of HIV infection. A reduction in the percentage of CD28-bearing CD4⁺ and CD8⁺ cell subsets was observed during the asymptomatic stage of the disease. This reduction was more pronounced in AIDS than in non-AIDS patients. At the same time, an increase in the absolute CD8⁺CD28⁻ cell number (greater in stage A than in stage B and C subjects) was observed in HIV-infected patients. The finding of an altered pattern of CD28 expression on T cells might per se explain certain early defects in the cytokine pattern and in the immune response peculiar to HIV-infected patients.