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.     

Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects.

The CD28 receptor on CD4+ and CD8+ T cells interacts with B7 molecules on antigen-presenting cells (APC) to generate essential costimulatory signals. The cytolytic potential of CD8+ T cells could be linked to CD28 expression. Since HIV induces dysfunction of both CD4+ and CD8+ T cells, we evaluated CD28 expression and function in both subsets during HIV infection. CD28 expression on CD8+ T cells from HIV+ subjects was strongly reduced in a disease stage-related fashion. CD28- CD8+ T cells preferentially expressed CD57 and CD11b, but lacked CD26 and IL-2R alpha. The CD8+ T cells from the patients showed a significantly reduced proliferative response to co-stimulation with cell-bound anti-CD3 and B7. Nevertheless, when stimulated with plate-fixed anti-CD3, CD8+ T cells from HIV-infected subjects proliferated normally, and normal levels of IL-2R alpha and transferrin-receptor could be induced on CD28- CD8+ T cells from the patients. In addition, stimulation with plate-fixed anti-CD3 induced proliferative responses in highly purified CD28- CD8+ T cells from both HIV- and HIV+ persons. Furthermore, the increased cytotoxic activity of peripheral blood mononuclear cells (PBMC) from HIV+ subjects, measured in an anti-CD3 redirected assay, was predominantly exerted by CD28- CD57+ T cells. CD4+ T cells from the patients showed a slight but significant CD28 down-regulation and were slightly hyporesponsive to B7 co-stimulation. Decrease of CD28 on CD8+ T cells from HIV+ subjects is associated with an impaired response to co-stimulation via B7. CD28- CD8+ T cells from seropositives, however, are not completely inert, since they contain in vivo activated CTL and they can be additionally activated through a B7-independent stimulation.     

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.     

Dichotomy of two CD8+ lymphocyte subsets in HIV infection. Depletion of CD8+ CD3- and expansion of CD8+ CD3+ subsets: consequence on the CD4/CD8 ratio.

In order to highlight the underlying mechanism(s) of the CD8 lymphocyte expansion in the HIV infection, two distinct CD8 subsets were analysed: T CD8bright+ CD3+ with MHC-restricted activity, and non-T CD8dim+ CD3-, which performs natural killer (NK) activity. It consists of a cross-sectional study including 168 HIV-infected patients (74 CDC stage II, 48 CDC stage III and 46 CDC stage IV) compared among them and to 60 healthy individuals. We observed an expansion of CD8+ CD3+ cells which masks a depletion of CD8+ CD3-. The comparative study showed that the expansion of the CD8+ CD3+ is relatively higher than that of total CD8+ lymphocytes and that the depletion of the CD8+ CD3- subset is severe, begins early and remains constant through the HIV progression. The comparison of CD4/CD8 and CD4/CD8+ CD3+ ratios showed that the latter could possibly be a better indicator in the HIV infection. The mechanism of inverted CD4/CD8 ratio in healthy individuals was also clarified. The CD8+ CD3+, CD8+ CD3- and CD4/CD8+ CD3+ parameters would be more specific markers than total CD8 and CD4/CD8 ratio especially in therapy trials.     

Concentrations of Soluble CD95 and CD8 Antigens in the Plasma and Levels of CD8+CD95+, CD8+CD38+, and CD4+CD95+ T Cells Are Markers for HIV-1 Infection and Clinical Status

Apoptosis mediated via the CD95 (FAS/APO-1) receptor is thought to play a role in the depletion of CD4+ T cells in HIV infection. In the present study expression of the CD95 antigen on lymphocyte subsets and the plasma level of soluble CD95 (sCD95) were determined in HIV-1-infected adults. The expression of CD95 was increased on CD8 cells in all groups of HIV+ individuals, while increased expression of CD95+ cells on CD4 cells was limited to individuals with CD4 counts of <200 mm³. The proportion of CD4+ that expressed CD95 was inversely correlated with the percentage of CD4+ PBL. The concentration of sCD95 was significantly higher in the plasma of HIV-infected individuals than in normal controls. The level of sCD95 in HIV-infected subjects showed no correlation with the percentage of PBL expressing CD95, indicating that the increased level of sCD95 did not reflect release from CD95+ PBL. The plasma sCD95 concentration was significantly correlated with the percentage of CD8+ cells and, particularly, with CD8+CD38– cells. A striking inverse correlation was found between the sCD95 plasma concentration and the proportion of CD4+CD95+ cells out of the total CD4+ population. There was no correlation between the serum level of sCD95 and that of soluble CD8 (sCD8), both of which were increased in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals was correlated with the percentage of CD95+ and CD8+CD38+ cells. The present study indicates that plasma sCD95 may be one of the factors that regulate apoptotic death of lymphocytes in HIV infection.     

Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity.

The CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics of the CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1+ remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.     

HIV感染后胃黏膜CD4+、CD8+T细胞数量分布及CD38表达的改变

目的 研究不同感染阶段HIV感染者胃黏膜中CD4+和CD8+T细胞数量和分布情况,及免疫细胞激活状态的改变.方法 有胃黏膜组织活检标本的HIV感染者42例,其中有明确临床分期诊断的36例,另选非HIV感染者胃黏膜组织活检标本10例为对照,利用免疫组织化学方法检测研究对象胃黏膜活检组织中CD4、CD8及CD38的表达,以图像分析系统分析其差异.结果 (1)AIDS患者胃黏膜中CD4+T细胞与对照组和无症状者相比,均显著减少(P(0.01),无症状者多数淋巴滤泡中仍有一定量CD4+T细胞,间质中多呈不均匀聚集分布,统计学与正常对照组差异无统计学意义(P>0.05);(2)HIV感染者胃黏膜内CD8+T细胞普遍噬腺体和黏膜上皮,部分病例胃黏膜内CD8+T细胞局部过度增生,与对照组相比,CD8+T细胞在感染者胃黏膜中显著增多(P<0.01),无症状者与AIDS患者CD8+T细胞差异无统计学意义(P>0.05);(3)在HIV感染者胃黏膜内,CD38阳性细胞主要分布于黏膜表层至浅1/3～2/3层,与对照组相比,HIV感染者胃黏膜中CD38表达增强(P<0.01),无症状者与MDS患者CD38表达差异无统计学意义(P>0.05).结论 HIV感染者胃黏膜中CD4+T细胞的数量和分布与疾病进展有密切联系,HIV对CD4+T细胞的感染和破坏导致黏膜免疫系统功能异常,可能是胃黏膜内CD8+T细胞数量增加,CD38表达增强的重要原因之一.     

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。     

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.     

Human Immunodeficiency Virus Type 1 Replication,Immune Activation, and Circulating CytotoxicT Cells Against Uninfected CD4+ T Cells

Cytotoxic T lymphocytes (CTL) that kill uninfected activated CD4⁺ T cells can be induced in vitro by stimulating CD8⁺ T cells with activated autologous CD4⁺ T cells. Similar CTL have been detected in circulating T cells from human immunodeficiency virus type 1 (HIV)-infected individuals. To define the in vivo correlates of this CTL activity, we studied plasma -2 microglobulin and HIV RNA levels, T-lymphocyte subset counts, and expression of CD28 on CD8⁺ T cells concurrently with circulating CTL activity against uninfected CD4⁺ T cells in 75 HIV-infected individuals at different stages of disease progression. Mean values of each parameter were compared in subsets of this group of 75 segregated on the basis of this CTL activity. The group with CTL against uninfected activated CD4⁺ T lymphocytes had more CD8⁺ T cells, a higher percentage of CD28^– CD8⁺ T cells, and higher plasma levels of HIV RNA and -2 microglobulin. CTL against uninfected activated CD4⁺ T cells were predominantly CD28^– and in HIV-infected individuals were associated with immunological or virological evidence of progressive disease. In HIV infection, circulating CTL activity against uninfected activated CD4⁺ T lymphocytes is associated with immune activation, CD8⁺ T cell expansion, accumulation of CD28^– CD8⁺ T cells, and inadequate suppression of HIV replication.     

慢性乙型肝炎患者CD4~+和CD8~+T细胞亚群的研究

目的:比较不同感染状态慢性乙型肝炎(CHB)患者外周血CD4+和CD8+T细胞亚群的差异。方法:收集CHB患者78例,根据感染状态分为乙型肝炎e抗原(HBeAg)阳性且肝功能正常、HBeAg阳性且肝功能异常和HBeAg阴性3组。13例健康志愿者(正常对照组)来自曙光医院体检中心。应用流式细胞术(FCM)检测不同感染状态CHB患者外周血中CD4+CD25+、CD8+CD28-、CD4+CD95+、CD8+CD95+细胞亚群的分布情况,并对各亚群分布情况与HBeAg和HBVD-NA水平的相关性进行分析。结果:与正常对照组相比,HBeAg(+)肝功能正常组的CD4+CD25+/CD4+和CD4+CD95+/CD4+明显升高(P<0.01,P<0.05),3个感染组CD8+CD28-/CD8+值均明显升高(P<0.01);与HBeAg(+)肝功能正常组相比,HBeAg(+)肝功能异常组和HBeAg(-)组的CD4+CD25+/CD4+明显降低(P<0.01),HBeAg(-)组CD8+CD95+/CD8+明显降低(P<0.05),HBeAg(+)肝功能异常组的CD8+CD95+/CD8+明显降低(P<0.01)。CD4+CD25+/CD4+,CD4+CD95+/CD4+与HBVDNA呈正相关(P<0.01,P<0.05),CD8+CD28-/CD8+与HBVDNA和HBeAg均呈正相关(P<0.01)。结论:CHB患者外周血中CD4+CD25+、CD8+CD28-T、CD4+CD95+细胞表达频率增加,可能对慢性乙肝病毒感染过程中的免疫耐受起一定作用。     

Increased expression of CD80, CD86 and CD70 on T cells from HIV-infected individuals upon activation in vitro: regulation by CD4+ T cells

T cells express CD28 and CD27 which transduce co-stimulatory signals after interaction with their ligands on antigen-presenting cells (APC). These ligands, CD80, CD86 and CD70, are also expressed to some extent on activated T cells. Here, we show that in human immunodeficiency virus (HIV)-infected individuals, CD28 and CD27 expression is decreased on CD8⁺ T cells. On the other hand, T cell stimulation in vitro induced high CD80, CD86 and CD70 expression on T cells from HIV-infected individuals. It appeared that an inverted CD4:CD8 T cell ratio could explain this enhanced expression of co-stimulatory ligands. Indeed, high expression levels of CD80, CD86 and CD70 were found on activated CD8⁺ T cells from HIV⁻ individuals cultured in the absence of CD4⁺ T cells. Addition of CD4⁺ T cells prevented this up-regulation. However, in HIV-infected individuals, addition of excess autologous or healthy control CD4⁺ T cells did not completely counteract up-regulation of co-stimulatory ligand expression on CD8⁺ T cells. Thus, to some extent, CD8⁺ T cells in HIV-infected individuals appeared to be refractory to CD4⁺ T cell-mediated regulation of ligand expression in vitro. Activated T cells from HIV-infected individuals and activated CD8⁺ T cells from healthy controls were able to act as accessory cells in CD3-induced T cell proliferation, which was dependent on cell-cell contact. Thus, we showed that T cells from HIV-infected individuals express enhanced levels of co-stimulatory ligands upon activation, which provides them with accessory cell properties. Enhanced stimulatory potential of these nonprofessional APC may contribute to persistently high levels of immune activation in HIV infection related to disease progression.     

T细胞凋亡受体和共刺激分子的表达变化与终末期肾功能衰竭患者细胞免疫功能的关系研究

目的：探究终末期肾功能衰竭患者T细胞亚群的凋亡受体CD95分子与共刺激分子CD28、CDl52（CTLA-4）的表达与细胞免疫功能的关系。方法：采用流式细胞术检测外周血T细胞的凋亡受体CD95（Fas）与共刺激分子CD28／CDl52表达。结果：终末期肾功能衰竭患者CD3^＋T细胞和CD4^＋T细胞比例明显高于健康对照组，CD4／CD8比值增加（P=0．008），CD4^＋T细胞和CD8^＋T细胞上CD95分子表达均上调（P=0．001），以CD8^＋T细胞上CD95分子增加更为明显；CD28和CD152分子在不同T细胞亚群上的表达均上调（P〈0．05），然而，CD4^＋T细胞以CD28分子表达增加为主，而CD8^＋T细胞则CD152分子表达增加为主。结论：终末期肾功能衰竭患者的细胞亚群失衡，共刺激分子CD28和CD152表达异常增加，提示T细胞活化与抑制性调节发生紊乱。T细胞亚群上凋亡受体CD95分子表达增加，以CD8^＋T细胞为主，说明终末期肾功能衰竭者淋巴细胞的减少可能通过两种途径——受体配体途径和负性共刺激分子CD152抑制信号途径，其中以CD8^＋T细胞减少为主，造成患者细胞免疫缺陷。     

Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection.

HIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CD8 lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any, between CTL activity and CD8 subpopulations. We have measured CTL activity against four HIV gene products (gag, tat, pol and env) and expression of CD45RO, CD45RA, HLA-DR, CD29, S6F1, and CD57 surface markers on CD8 cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HIV-gag, -pol and -tat, and the other to HIV-pol. All the HIV-infected and two uninfected children had abnormal proportions of CD8 subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CD8 subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CD8 cells, an expansion of HLA-DR+ CD8 cells and a loss of CD45RA+ CD8 cells.     

Enhanced expression of CTLA-4 (CD152) on CD4+ T cells in HIV infection

CTLA-4 (CD152) is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has an essential inhibitory function in maintaining the homeostasis of the immune system. Down-regulation of CD28 predominantly on CD8+ T cells has been described in HIV infection, but analysis of CTLA-4 is complicated by its low expression levels. Here we have used potent signal enhancement to study CTLA-4 on peripheral blood mononuclear cells (PBMC) during HIV infection. CTLA-4 was expressed only on T cells. Expression levels were significantly increased selectively on CD4+ T cells during all stages of HIV infection, while CTLA-4 expression on CD8+ T cells was always low. In contrast, after stimulation with the mitogen phytohaemagglutinin (PHA), CTLA-4 levels were strongly increased on T cells from controls but in T cells from HIV patients this response was severely impaired. Our data suggest that in HIV infection CD4+ and CD8+ T cells may be less responsive to B7 costimuli due to two different mechanisms: increase in CTLA-4 expression by CD4+ cells and down-regulation of CD28 by CD8+ cells.     

HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the alpha/beta T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells.     

CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft recipients: expansion of an uncommon CD8+ CD57- subset and its progressive replacement by CD8+ CD57+ T cells.

Allograft recipients undergoing cytomegalovirus infection present increased proportions of circulating CD8+ lymphocytes. A longitudinal study of 11 kidney and five liver allograft recipients with primary CMV infection but no other etiological factor of graft dysfunction revealed selective imbalances of peripheral blood CD8+ T cell subsets. Initially, CMV viraemia is associated with elevated CD8+bright T cell numbers and T cell activation. Activation markers fall to normal when viral cultures become negative (before the end of the first month). During the second to sixth month, most (12/16) patients keep up high CD8+ T cell counts (1050-2900 CD8+ cells/mm3), comprising an uncommon CD8+ T cell subset, as 45-73% of CD8+bright lymphocytes were CD3+ and TCR alpha beta+, but were not stained by anti-CD28, CD11b, CD16, CD56, and CD57 antibody. Unexpectedly, CD8+CD57+ T cells, a hallmark of CMV infection, do not appear until the second to sixth month of primary CMV infection, and their numbers increase progressively thereafter. They become the predominant CD8+ T cell subset after 6 months of infection and their persistence for several (up to 4) years is strongly correlated (r = 0.87) with expansion of CD8+ cells. By analysis with MoAbs, there was no bias towards the use of particular TCR-V beta gene families at any time of primary CMV infection. Persistence of CD8 lymphocytosis is thus directly related to the rate of expansion of an uncommon CD8+CD57- subset and its progressive replacement by CD8+CD57+ T cells that are chronically elicited by CMV.     

传染性非典型肺炎患者CD4阳性T细胞在发病早期显著下降

为了解传染性非典型肺炎患者早期的免疫状态 ,采用流式细胞仪以三色荧光标记的单克隆抗体 (CD4 FTTC/CD8 PE/CD3 PC5 )检测入院时 30例非典型肺炎或疑似患者的外周血T细胞亚群比例 ,并作绝对计数和计算CD4 +/CD8+比值。结果表明 ,11例非典型肺炎患者的CD3+、CD4 +T淋巴细胞比例、CD4 +/CD8+比值和CD3+、CD4 +和CD8+T淋巴细胞计数均明显低于 34例健康人 (P <0 0 0 1)。如CD4 +T细胞比例从健康人的 4 0 6 %降至 14 5 % ,细胞计数从健康人的 712 1/mm3 降至 15 1 1/mm3。患者CD8+T淋巴细胞比例也有一定程度的下降 (从健康人的 2 8 7%降至 2 2 6 % ,P <0 0 5 )。 19例疑似患者的上述大部分指标亦较健康人群有明显降低 (P <0 0 0 1)。非典型肺炎患者组与疑似患者组比较 ,前者CD3+T细胞和CD4 +T细胞比例进一步下降 (P <0 0 1) ,CD4 +/CD8+比例也倒置至 0 70。患者病程早期CD4 +T细胞比例下降可引起T细胞免疫功能低下 ,表明非典型肺炎和免疫功能失调有关。