哮喘患者支气管肺泡灌洗液和外周血CD_4~＋T细胞活化与白细胞介素-5释放水平的观察

为探讨Ｔ淋巴细胞功能异常与哮喘发病的关系，对１２例过敏性哮喘患者、１０例非过敏性哮喘患者、９例非哮喘过敏患者和１０例正常人的支气管肺泡灌洗（ＢＡＬ）液细胞和外周血单个核细胞（ＰＢＭＣ），分别在有无过敏原刺激条件下在体外进行培养，观察辅助（ＣＤ＋４）Ｔ细胞活化状态和白细胞介素（ＩＬ）－５释放水平。结果表明，过敏性与非过敏性哮喘组ＢＡＬ液细胞和ＰＢＭＣ在无刺激培养条件下，ＣＤ＋４Ｔ细胞活化数量及释放ＩＬ－５水平均显著增高；过敏性哮喘组患者Ｔ细胞对过敏原的反应性明显高于非过敏性哮喘组（Ｐ值均＜０．０１）；非哮喘过敏症组患者ＰＢＭＣ在过敏原刺激下，ＣＤ＋４Ｔ细胞活化数量和上清液ＩＬ┐５含量显著增加，但其ＢＡＬ液细胞在过敏原刺激下培养，释放ＩＬ┐５水平仍然显著低于两哮喘组（Ｐ值均＜０．０１）。研究表明，支气管┐肺局部ＣＤ＋４Ｔ细胞活化程度和ＩＬ┐５释放能力在哮喘发病中起重要作用。     

哮喘患者辅助T细胞活化与白细胞介素5释放

目的 了解过敏状态和哮喘状态下辅助（ＣＤ４＾＋）Ｔ细胞活化及白细胞介素５（ＩＬ－５）释放的原因和作用。方法 对过敏性哮喘组１２例（ＡＡ）、非过敏性哮喘组１０例（ＮＡＡ）、过敏性非哮喘组９例（ＡＮ）及正常对照组１０名（Ｎ）在有无抗原刺激下进行支气管肺泡灌洗液（ＢＡＬＦ）细胞及周围血单个核细胞（ＰＢＭＣ）培养，比较组内和组间ＣＤ４＾＋Ｔ细胞活化（标志物ＣＤ２５＾＋）与ＩＬ－５释放水平。结果 ＰＢＭＣ在     

老年人淋巴细胞表面抗原变化及RgI的刺激效果

用免疫荧光方法研究４７名健康老人和１４名健康青年人淋巴细胞表面抗原ＣＤ２５、ＣＤ４５ＲＡ及ＣＤ４５ＲＯ的分布。结果表明青、老年人淋巴细胞活化前的ＣＤ＾＋２５细胞皆较低而无显著差别，但经ＰＨＡ或ＰＨＡ＋人参皂甙刺激后都升高。然而，老年人比青年人增长幅度小，回降较慢。老年人的ＣＤ４５ＲＯ＾＋细胞多于ＣＤ４５ＲＡ＾＋细胞。青、老年人的ＣＤ４５ＲＡ＾＋／ＣＤ４５ＲＯ＾＋比值分别为０．９１和０．６６。说明Ｒ     

旋毛虫感染小鼠IgG,IL—2和T淋巴细胞亚群动态变化的 …

目的 了解小鼠感染旋毛虫后ＩｇＧ抗体水平、ＩＬ－２分泌量和Ｔ淋巴细胞亚群的动态变化。方法 分别于旋毛虫感染后第７、１４、２１、２８和３５天,采用ＥＬＩＳＡ方法检测血甭特异性ＩｇＧ抗体水平和ＩＬ－２含量,采用流式细胞仪检测ＣＤ４＾＋、ＣＤ８＾＋Ｔ细胞百分率。结果 ＩｇＧ抗体水平在感染后逐渐上升,感染后３５天达最高值;Ｔ淋巴细胞的变化表现为ＣＤ４＾＋细胞减少、ＣＤ８＾＋Ｔ细胞增多,ＣＤ４＾＋／ＣＤ８＾     

哮喘患者外周血T淋巴细胞凋亡及其分子机制

目的　探讨哮喘患者外周血 Ｔ淋巴细胞凋亡率的变化及其分子机制。方法　取１２ 例急性发作期哮喘患者（ 哮喘组） 及１０ 名正常对照者（ 对照组） 外周血淋巴细胞并无菌分离 Ｔ 淋巴细胞,采用电镜和原位末端终止法（ Ｔ Ｕ Ｎ Ｅ Ｌ） 观察抗 Ｃ Ｄ＋３ 单抗（１００ ｍｇ／ Ｌ） 诱导体外培养０ 、２４ 、４８ 、７２ 小时后 Ｔ淋巴细胞凋亡变化,同时采用细胞原位杂交法观察不同培养时间 Ｔ 淋巴细胞 Ｂｃｌ２ ｍ Ｒ Ｎ Ａ 及 Ｂａｘｍ Ｒ Ｎ Ａ表达变化。结果　正常组及哮喘组 Ｔ 淋巴细胞抗 Ｃ Ｄ＋３ 单抗诱导后均出现凋亡典型形态改变,哮喘患者外周血 Ｔ细胞经抗 Ｃ Ｄ＋３ 单抗诱导２４ 小时后凋亡率为（９１９ ±２２５） ％ ,４８ 小时为（１５８９ ±２１８） ％ ,７２ 小时为（２１３７ ±３２４） ％ ;与正常组２４ 小时（１７９ ±２２２） ％ 、４８ 小时（２５２５ ±３５３） ％ 、７２ 小时（３５１４ ±２５３） ％ 比较,差异有显著性（ Ｐ 均＜ ００１） ,哮喘组７２ 小时方接近正常组２４ 小时水平。哮喘组 Ｔ 淋巴细胞凋亡抑制基因 Ｂｃｌ２ ｍ Ｒ Ｎ Ａ 的表达各时相均与正常组比较,差异有显著性（ Ｐ＜ ００１） 。而凋亡促进基因     

哮喘患者支气管肺泡灌洗液和外周血CD4^＋T细胞活化与白细胞介…

为探讨Ｔ淋巴细胞功能异常与哮喘发病的关系，对１２例过敏性哮喘患者、１０例非过敏性哮喘患者、９例非哮喘过敏患者和１０例正常人的支气管肺泡灌洗液细胞和外周血单个核细胞，分别在有无过敏原刺激条件下在体外进行培养，观察辅助Ｔ细胞活化状态和白细胞介素释放水平。结果表明，过敏性与非过敏性哮喘组ＢＡＬ液细胞和ＰＢＭＣ在无刺激培养条件下，ＣＤ４＾＋Ｔ细胞活化数量及释放ＩＬ－５水平均显著增高；过敏性哮组患者Ｔ细胞过     

强直性脊柱炎患者外周血Th1／Th2淋巴细胞类型

目的 通过检测强直性脊柱炎患者外周血中ＣＤ４＾＋和ＣＤ８＾＋Ｔ淋巴细胞分泌细胞因子的情况,探讨Ｔ淋巴细胞亚群与强直性脊柱炎发病的关系。方法 建立三色流式细胞分析法对强直性脊柱炎患者和健康志愿者外周血中淋巴细胞的胞内细胞因子（ＩＦＮγ、ＩＬ－４）和表面抗原（ＣＤ４、ＣＤ８）进行分析。同时采用夹心酶联免疫吸附法测定血清中ＩＦＮγ和ＩＬ－４的水平。结果 无论是ＣＤ４＾＋还是ＣＤ８＾＋ＡＴ淋巴细胞,分泌Ｉ     

内皮素和一氧化氮平衡在哮喘犬发病机制中的作用

目的 探讨内皮素（ＥＴ）和一氧化氮（ＮＯ）平衡失调在支气管哮喘（简称哮喘）发病机制中的作用。方法 吸入猪蛔虫抗原复制过敏性哮喘犬模型，随机将实验动物分为五组，即对照组（Ａ组，６只），哮喘组（Ｂ组，６只）生理盐水＋哮喘组（Ｃ组，６只）Ｎ＾Ｇ－单甲基左旋精氨酸（Ｌ－ＮＭＭＡ）＋哮喘组（Ｄ组，６只）和左旋精氨本－ａｒｇ）＋哮喘组（Ｅ组，６只），观察了ＥＴ－１和ＮＯ对犬气道平滑肌的影响。结果 ＥＴ－１使呼     

CD23与支气管哮喘

ＣＤ２３是ＩｇＥ的低亲和力受体，主要在Ｂ细胞、嗜酸粒细胞（ＥＯＳ）、激活的单核／巨噬细胞、血小板、滤泡树突状细胞、郎罕氏细胞、表皮角细胞、胸腺上皮细胞、部分Ｔ细胞、自然杀伤细胞等细胞膜上表达。血清中存在可溶性ＣＤ２３（ｓＣＤ２３）。它们与支气管哮喘关系密切，在细胞间粘附、抗原的呈递、Ｔ和Ｂ细胞的活化、ＩｇＥ合成、哮喘相关基因的转录等过程中可能发挥重要作用。     

地塞米松对哮喘患者IL—4,IL—5及IgE合成的抑制作用观察

观察了地塞米松（Ｄｅｘ）对哮喘患考外周血单个核细胞（ＰＢＭＣ）合成白介素－４（ＩＬ－４）、白介素－５（ＩＬ－５）和免疫球蛋白Ｅ（ＩｇＥ）的抑制作用。结果证明，哮喘１组（仅用植物血凝素，简称ＰＨＡ）ＰＢＭＣ合成ＩＬ－４、ＩＬ－５、ＩｇＥ较对照组（仅用ＰＨＡ）明显增高（Ｐ＜０．０１），哮喘２组（ＰＨＡ＋Ｄｅｘ）ＰＢＭＣ合成ＩＬ－４、ＩＬ－５、ＩｇＥ较哮喘１组显著下降（Ｐ＜０．０５）。认为Ｄｅｘ治疗哮喘的机理，部分是通过减少ＩＬ－４ＩＬ－５、ＩｇＥ的合成而达到抗炎的目的。     

Asthma severity is associated with an increase in both blood CXCR3+ and CCR4+ T cells

OBJECTIVES: A predominance of type 2 helper T cells (Th2) in the bronchoalveolar space and peripheral blood is a well-accepted feature of bronchial asthma. However, the relationship between peripheral blood Th2 cells and asthma severity has not been thoroughly investigated. METHODS: As Th1 cells predominantly express the chemokine receptor CXCR3 and Th2 cells express CCR4, we assessed the distribution of peripheral blood CXCR3+ and CCR4+ lymphocytes using flow cytometry in 186 patients with asthma and 75 normal subjects. RESULTS: The proportion of CXCR3+/CD45RO+ cells in CD4+ T cells increased as the severity of asthma increased. The percentage of CCR4+/CD45RO+ cells in CD4+ T cells were elevated in mild to severe asthma patients compared with controls. However, there was no significant difference in CCR4+/CD45RO+ cells between the mild to severe asthma patients. There was no relationship between the patient's age and the numbers of CXCR3+ or CCR4+ T cells. The percentage of CCR4+ cells in CD45RO+/CD4+ T cells correlated with the levels of total serum IgE (r = 0.630, P < 0.0001). CONCLUSIONS: The proportion of CCR4+ cells in blood memory helper T cells may be increased in patients with asthma and is associated with the level of serum IgE, but severity of asthma is also associated with the increase of blood CXCR3+ cells in memory helper T cells.     

A low blood lymphocyte count is associated with an expansion of activated cytotoxic lymphocytes in patients with B-cell chronic lymphocytic leukaemia

Abstract: In order to determine the relationships between CD2+ lymphocyte subpopulations and tumour mass, the immunophenotype of natural killer (NK) cells and T lymphocyte subsets was studied in 56 B-chronic lymphocytic leukaemia (B-CLL) patients and 38 healthy subjects. The patients were classified according to their blood lymphocyte count (BLC). Forty patients had BLC<30×10⁹/l (low BLC, less tumour mass) and 16 patients had BLC>30×10⁹/l (high BLC, larger tumour mass). The percentage of CD3^– CD56+ cells, as well as of CD8+, CD8+CD45RO+ and CD3+CD57+ T subsets in low BLC patients, were higher than those found in high BLC patients. Conversely, the percentages of CD3+HLA DR+, CD4+ and CD4+CD45RO+ lymphocytes were higher in high BLC patients than in low BLC patients. The CD4/CD8 ratio was decreased in low BLC patients while it was increased in high BLC patients and a significant positive correlation was found between their CD4/CD8 ratio and their BLC. We conclude that in low BLC B-CLL patients there is a decreased percentage of activated helper lymphocytes and an increased percentage of NK cells and activated cytotoxic T lymphocytes. These results suggest a role for NK cells, and helper and cytotoxic T lymphocytes in the control of tumour burden in B-CLL patients.     

CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease

The pathogenesis of coronary arterial inflammation in acute Kawasaki disease (KD) is unclear. To test the hypothesis that the KD vascular lesion is an activated T lymphocyte-dependent process, immunohistochemical studies were done on coronary artery aneurysms from 8 fatal acute KD cases by using antibodies to CD45RO (activated or memory T lymphocyte), CD8 (cytotoxic T lymphocyte), CD4 (helper T lymphocyte), HAM56 (macrophage), and CD20 (B lymphocyte). Acute KD coronary arteritis was characterized by transmural infiltration of CD45RO T lymphocytes with CD8 T lymphocytes predominating over CD4 T lymphocytes. Macrophages were present primarily in the adventitial layer; B lymphocytes were notably absent. These data lend support to the hypotheses that KD results from infection with an intracellular pathogen, such as a virus, whose antigens are presented by major histocompatibility complex class I molecules, and that CD8 T lymphocytes and macrophages are important in the pathogenesis of KD coronary aneurysms.     

A comparison of the expression of lymphocyte activation markers in blood, bronchial biopsies and bronchoalveolar lavage: evidence for an enrichment of activated T lymphocytes in the bronchoalveolar space.

In this study healthy never-smoking subjects (n = 18) were recruited from a population study. Bronchoalveolar lavage (BAL), blood lymphocytes and bronchial biopsies, analysed both in the epithelium and lamina propria, were stained for T and B lymphocytes, natural killer (NK) cells and different subpopulations of T lymphocytes. In BAL, significantly higher proportions of T lymphocytes (CD3), T lymphocyte activation markers; HLA-DR, CD26+, CD49a+, CD54+ and CD69+, helper T (CD3+4+) and memory helper T lymphocytes (CD4+45RO+29+) and memory T lymphocytes (CD3+45RO+) were found, compared to blood. However, the proportion of IL-2 receptor-positive T lymphocytes (CD25+) was lower in BAL than in blood. A previously described higher ratio of CD3+4+/CD3+8+ in BAL than in blood (3.4 vs 1.7; P = 0.001) was confirmed. In bronchial biopsies, we found significantly higher numbers of CD8+ cell profiles per mm2 in the epithelial compared to the lamina propria compartment. We conclude that healthy never-smoking men have higher levels of activated memory T lymphocytes in BAL than in blood, and that the T-cell subpopulations differ in the epithelial compared to the lamina propria compartment in the bronchial mucosa and these compartments should be analysed separately. It is reasonable to think that there is a gradient from blood to the airway lumen where T cells are recruited from blood to take part in the defense towards damaging agents.     

病毒性心肌炎患者外周血T淋巴细胞亚群及B淋巴细胞的研究

目的: 测定不同时期病毒性心肌炎(VMC)患者T淋巴细胞亚群及B淋巴细胞的数量,并同时检测患者血清心肌损害标志物心肌肌钙蛋白I(cTnI)的水平,探讨其在VMC发病机制中的作用。方法: 采用流式细胞术检测不同时期VMC患者(n=126)外周血CD4+CD45RA+和CD4+CD45RO+以及CD19+的表达,并设正常人群作为对照组(n=50)。结果: 急性期（<3个月）患者CD4+CD45RA+和CD4+CD45RO+以及CD19+与对照组相比差异显著。<1个月以CD4+CD45RA+和CD4+CD45RO+为著（P<0.01;P<0.01）。病程<7 d的患者与对照组相比,CD4+CD45RA+值的降低具有显著性(P<0.01);CD4+CD45RO+值下降明显(P<0.01)。而病程7~14 d、14~21 d及21~30 d的患者CD4+CD45RA+值、CD4+CD45RO+值及CD19+值与对照组相比差异均有统计学意义,CD4+CD45RO+值恢复较快。CD4+CD45RA+/CD4+CD45RO+在发病14 d内的患者与对照组差异无统计学意义;而14~30 d的患者与对照组相比差异有显著性。发病1~3个月患者以CD19+为著（P<0.01）。急性期CD4+CD45RA+/CD4+CD45RO+细胞的比例失衡。恢复期（3~12个月）患者CD4+CD45RA+和CD4+CD45RO+以及CD19+、CD4+CD45RA+/CD4+CD45RO+细胞的比例与对照组相比差异无显著性。结论: VMC患者感染初期（<1个月）以T淋巴细胞亚群异常为主,感染后期（1~3个月）以B淋巴细胞异常较为显著,以上两时期均存在CD4+CD45RA+/ CD4+CD45RO+细胞比例失衡。恢复期（3~12个月）T淋巴细胞及B淋巴细胞逐渐恢复至正常。     

Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma

IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE+ cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3+, CD4+, and CD8+ T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.     

Increase in CD95 (Fas/APO-1)-positive CD4+ and CD8+ T cells in peripheral blood derived from patients with autoimmune hepatitis or chronic hepatitis C with autoimmune phenomena

BACKGROUND: The expressions of CD95 (Fas/APO-1) and Bcl-2 are determinants of apoptosis in normal lymphocytes, and abnormalities in their expressions might contribute to the induction of autoimmunity. In this study, we examined the expressions of CD95 and Bcl-2 on freshly isolated T and B cells from patients with autoimmune hepatitis (AIH) or chronic hepatitis C associated with autoimmune phenomena (CH-C(AI)). METHODS: The CD95 and Bcl-2 expressions within CD4+ T, CD8+ T, and CD19+ B cell subsets were analysed by two-colour flow cytometry. RESULTS: The surface expression of CD95 was significantly high in both the CD4+ T and CD8+ T cell subsets derived from the patients with AIH and those with CH-C(AI), compared with expression in patients with CH-C and normal subjects. The increase in CD95 expression was associated with the phenotypic conversion of naive CD45RO- to primed CD45RO+ CD4+ T cells. Bcl-2 was detected in the vast majority of peripheral T and B cells. There was no significant difference in the percentage of Bcl-2-positive cells in the CD4+ T cell, CD8+ T cell and CD19+ B cell subsets among the patient groups and normal subjects. CONCLUSIONS: These results indicate that an increase in CD4+ T cells expressing CD45RO and CD95 marks an important subset of AIH and CH-C(AI) patients. These expanded CD95+ CD45RO+ primed T cells most likely reflect a continuous antigen-specific or non-specific activation of T lymphocytes, and/or the persistent presence of activated lymphocytes as a consequence of abnormalities in the peripheral deletion of activated lymphocytes. These persistently activated lymphocytes might play a role in the induction of autoimmunity in AIH and CH-C(AI).     

低亲和力IgE受体与外源性支气管哮喘

本文对３０例外源性哮喘患者及３０例正常人的外周血单个核细胞（ＭＮＣ）低亲和力ＩｇＥ受体（即ＣＤ２３）表达、白细胞介素－４（ＩＬ－４）及血清ＩｇＥ水平进行测定。结果显示：发作组哮喘患者ＩｇＥ、ＩＬ－４、ＣＤ２３与缓解组及正常对照组之间有显著性差异（Ｐ＜０．０１）。且ＩｇＥ升高与ＣＤ２３呈正相关（ｒ＝０．８２７；Ｐ＜０．０１）。缓解组ＩｇＥ抗体、ＩＬ－４与正常对照组之间无显著性差异（Ｐ＞０．０５）；ＣＤ２３与正常对照组之间有显著性差异（Ｐ＜０．０ｌ）。以上结果表明了这一细胞因子的失衡与外源性哮喘的关系。     

Absence of bcl-2 expression by activated CD45RO+ T lymphocytes in acute infectious mononucleosis supporting their susceptibility to programmed cell death

bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death (apoptosis). There is now increasing evidence that regulation of bcl-2 expression is a determinant of life or death in normal lymphocytes. We have recently described that activated (CD45RO+) CD4+ and CD8+ T cells in acute infectious mononucleosis (IM) undergo apoptotic cell death on culturing, indicating an activation-driven cell death of mature T cells. In this work, we examine bcl-2 expression by activated T cells in acute IM using a flow-cytometric analysis with an anti-bcl-2 monoclonal antibody (MoAb). It was consistently observed that most T cells from acute IM patients displayed only much less bcl-2, while normal T cells expressed bcl-2 relatively strongly. Multicolor analysis showed that bcl-2- lacking T cells in acute IM were restricted to the CD45RO+ (activated) populations of CD4+, as well as CD8+ T cells. In contrast, the relatively intense levels of bcl-2 were expressed in both CD45RO+ and CD45RO- T-cell populations from normal subjects. This marked difference in bcl-2 expression of CD45RO+ T cells between acute IM and normal controls was also confirmed by Western blot analysis. Activated (CD45RO+) T cells with low bcl-2 expression, but not bcl-2-expressing CD45RO- T cells, in acute IM patients were found to die easily when cultured without added growth factors. However, in normal individuals, both CD45RO+ and CD45RO- T cells were relatively stable on culturing. These findings suggest that lack of bcl-2 expression by activated (CD45RO+) T cells in acute IM might be associated with their susceptibility to programmed cell death.     

CTLA4-Ig对老年支气管哮喘病人CD4+ CD45 RO+ T细胞功能的影响

目的研究老年支气管哮喘病人周围血CD4 CD45RO T细胞表达IL-4及IL-13的情况及CTLA4-Ig对其影响。方法用ELISA方法测定老年支气管哮喘病人CD4 CD45RO T细胞产生IL-4和IL-13的水平及CTLA4-Ig对其影响。结果老年支气管哮喘病人CD4 CD45RO T细胞分泌IL-4、IL-13增多,IL-13增多较IL-4更为明显(P<0.01),CTLA4-Ig可有效抑制老年哮喘病人CD4 CD45RO T细胞分泌IL-4和IL-13(P<0.01)。结论CD4 CD45RO T细胞产生的IL-4和IL-13在老年哮喘发病中起重要作用,CTLA4-Ig可有效抑制IL-4和IL-13的分泌。