生长激素分泌过多患者外周血淋巴细胞CD2mRNA的表达

应用ＲＮＡ斑点杂交法，测定了１２例生长激素（ＧＨ）分泌过多患者及１０例正常人外周血淋巴细胞ＣＤ２ｍＲＮＡ的表达，发现患者ＣＤ２ｍＲＮＡ的表达较之正常人有显著下降，提示ＧＨ分泌过多对Ｔ淋巴细胞ＣＤ２ｍＲＮＡ的表达有显著影响。此结果为研究内分泌系统产生的肽类激素对免疫系统的影响提供了新资料。     

IL-2对人外周血淋巴细胞FAP-1 mRNA表达的影响

Fas系统引起的细胞凋亡是成熟T细胞激活诱导的细胞死亡(Activation induced cell death,AICD)的主要机制[1],这一过程受到多种正负因素的严密调节,Fas相关磷酸酯酶(Fas-associated phosphatase,FAP-1)是一种重要的负性调节因子[2,3].本研究通过观察IL-2对活化外周血淋巴细胞FAP-I mRNA表达水平的影响,揭示AICD过程分子调控机制,为进一步研究淋巴细胞凋亡的分子调节机制提供新的理论基础.     

IL-2调节人外周血T淋巴细胞CTLA-4表达

目的 探讨人外周血T淋巴细胞CTLA-4的表达情况及IL-2对其表达的调节作用。方法 采用流式细胞仪定量测定人外周血T淋巴细胞内及细胞膜上CTLA-4的水平，半定量RT-PCR检测T淋巴细胞内CTLA-4mRNA的水平，并在体外用IL-2刺激T淋巴细胞后观察CTLA-4及CTLA-4mRNA水平的变化。结果 人外周血T淋巴细胞膜表面几乎不表达CTLA-4，7．6％-18．0％的T淋巴细胞有胞内表达，CD4^ T淋巴细胞表达CTLA-4的阳性比例略高于CD8^ T淋巴细胞；人T淋巴细胞可溶性形式的CTLA-4mRNA半衰期短于全长CTLA-4mRNA；IL-2可以通过诱导人T淋巴细胞CTLA-4mRNA的转录上调CTLA-4的表达，IL-2诱导的细胞多为CD25^ T淋巴细胞。结论 CTLA4多存在于人外周血T淋巴细胞内，参与T淋巴细胞活化过程的调节。IL-2的免疫抑制作用可能与其诱导T淋巴细胞内CTLA-4mRNA转录，从而上调CTLA-4的表达有关。     

肺癌患者外周血T淋巴细胞及亚群CD28表达和活化的改变

目的检测共刺激分子CD28在肺癌患者外周血T淋巴细胞及亚群中的表达密度和细胞活化程度的变化,并探讨该变化与肺癌临床分期的关系.方法用三色荧光直标流式细胞法分别检测38例正常人与42例肺癌患者中血T淋巴细胞亚群中CD28的阳性率以及CD28+T淋巴细胞亚群活化率.结果与正常人相比,肺癌患者外周血中的CD3+CD28+,CD4+CD28+,CD8+CD28+淋巴细胞百分比均有下降(P＜0.05).淋巴细胞及其T亚群中的CD25+CD28+,CD38+CD28+淋巴细胞百分比亦有所下降(P＜0.05),但在不同临床分期的患者之间无显著性差异(P＞0.05).结论肺癌患者外周血T淋巴细胞的CD28表达密度及CD28+T细胞的活性均有降低,但下降幅度与临床分期无关.     

人外周血抗CD3单克隆抗体激活的杀伤细胞系的建立

诱导和维持T细胞抗肿瘤的免疫疗法．最近有了新的认识。T细胞被活化还是产生耐受．有赖于肿瘤特异性抗原产生的部位和时机。在肿瘤发生的局部．T细胞失能或被清除．或者转移的瘤细胞与T细胞“隔离”使肿瘤抗原不能被T细胞识别而产生耐受。T细胞介导的特异胜免疫应答．在机体抗肿瘤过程中起主要作用，必须打破其免疫耐受才有     

人外周血淋巴细胞CD23分子表达研究

应用荧光标记的流式细胞分析技术，研究正常人外周血淋巴细胞膜表面ＣＤ２３表达。结果显示：外周血单个核细胞中ＣＤ２３＋细胞约占６％；Ｂ淋巴细胞中ＣＤ２３＋细胞比例最高为１６％左右；Ｔ淋巴细胞中有时也有１～２％的阳性检出率；ＰＭＡ活化后的Ｂ细胞中，ＣＤ２３＋细胞比例随刺激时间增加而升高，最高可达７０％；ＰＨＡ活化的Ｔ细胞中，ＣＤ２３＋细胞比例也可增加至１０％。从而表明，外周血中ＣＤ２３＋细胞主要分布于Ｂ细胞群中，活化能显著诱导ＣＤ２３分子在Ｂ细胞上的表达。活化后的Ｔ细胞也能部分表达ＣＤ２３分子。     

HBV感染PBMC后对宿主细胞CD25 mRNA表达的影响

HBV除对肝细胞具有高度亲和性外，还可侵犯外周血单个核细胞（PBMC）,这不仅是HBV肝外感染的直接证据，也是HBV潜伏或隐匿的场所。CD25是IL-2Rα链，主要存在于T淋巴细胞表面，是T淋巴细胞活化的标志，在抗病毒免疫反应中起重要作用。为探讨HBV感染PBMC后对宿主细胞CD25mRNA表达的影响，本文选择249例慢性乙肝患者进行观察，现将结果报道如下。     

探讨乙肝患者外周血淋巴细胞的表达

淋巴细胞不同亚群对病毒抗原的应答反应不同,对乙型肝炎的进展的影响也不同。本文采用流式细胞技术（FACS）,对乙型肝炎患者外周血CD3＋T细胞、CD4＋T细胞、CD8＋T细胞、CD16＋CD56＋（NK细胞）、CD19＋（B细胞）进行检测。并探讨HBV感染后乙型肝炎患者的细胞免疫状态与疾病发展的关系。     

手足口病患者外周血淋巴细胞亚群激活与CD95表达的检测与意义

目的 研究手足口病（HFMD）患者外周血淋巴细胞CD95、HLA-DR活化分子表达的变化及其意义.方法 以健康儿童作为对照,采用流式细胞术,检测58例手足口病患者外周血淋巴细胞CD95标志、T细胞亚群及其HLA-DR抗原表达.结果 HFMD患者外周血CD3^＋T细胞的百分率（63.82±7.74）%与健康对照组比较差异有统计学意义（P〈0.001）,CIM^＋T细胞的百分率（34.29±7.33）%明显低于正常对照组（P〈0.005）;HLA-DR^＋淋巴细胞（28.30±7.61）%比正常对照组显著增高（P〈0.005）;CD8^＋T细胞表达HLA-DR水平（1.34±1.12）%明显高于对照组（P〈0.005）;淋巴细胞CD95表达差异无统计学意义（P〉0.05）.结论 HFMD患者存在细胞免疫功能紊乱和淋巴细胞异常激活现象,T淋巴细胞的激活以CD8^＋T细胞为主,其在抗病毒感染中起着重要作用.     

CD28 mRNA rapidly decays when activated T cells are functionally anergized with specific peptide

The induction of non-responsiveness in specific clones of Tcells In vivo might be expected to reverse immunologlcally mediateddisease processes. With this goal in mind, experiments in vitrowith cloned T cells have investigated the mechanisms of inductionof anergy. Resting T cells can be functionally inactivated invitro by high doses of appropriate peptide in either the presenceor absence of antigen presenting cells. During the inductionof anergy, the modulation of the surface phenotype of T cellsis similar to that of cells proliferating in response to animmunogenic stimulus. The amount of T cell receptor at the cellsurface is down regulated, whereas the CD2 and CD25 receptorsare increased in density. in contrast, CD28 has been identifiedas a membrane protein that is differentially regulated duringactivation and the induction of non-responsiveness. Ligatlonof CD28 provides an efficient costlmulatory signal for activationof T cells. In this report, we show that not only resting cells,but also fully activated T cells can be rendered non-responsiveand that this process is accompanied by profound downregulationof CD28, both at the level of cytoplaamic mRNA and surface expressionof the mature protein. This observation anticipates clinicalintervention in immunologically mediated disease, where thetarget T cells are more likely to be activated than in a restingstate.     

B cells regulate expression of CD40 ligand on activated T cells by lowering the mRNA level and through the release of soluble CD40

The expression of CD40 ligand (CD40L) on activated T cells (CD4⁺ T cell clone MT9) is diminished when the T cells are cultured in the presence of B cells. This effect, observed both with normal tonsil B cells and with the B cell line JY, was detected after 6 h and sustained at least until 18 h of co-culture. Analysis of mRNA showed that CD40L mRNA levels were not modified after 6 h, but were significantly down-regulated after 18 h of co-culture with B cells. Although CD40L expression could not be detected by a CD40-Fc chimera, the molecule was still expressed at the membrane as shown with a polyclonal antiserum against CD40L (anti-TRAP). In addition, T cells activated in the presence of B cells were stained by a polyclonal antiserum against CD40, without the appearance of CD40 mRNA. These results indicated that a soluble form of CD40 (sCD40) bound to the expressed CD40L on T cells. The existence of sCD40 was confirmed by detection of sCD40 in B cell supernatants using a specific enzyme-linked immunosorbent assay. Collectively, these data show that B cells can regulate the expression of CD40L on activated T cells at least by two different mechanisms.     

Enhancement of proliferation and downregulation of TRAIL expression on CD8+ T cells by IL-21

Mounting evidence indicates that the cytokine IL-21 can significantly enhance the survival of CD8(+) T lymphocytes. Given that CD4(+) T lymphocytes constitute the main cellular source for IL-21 in vivo, it is tempting to speculate a direct role in mediating the "help" provided by these CD4(+) T cells to the CD8 response. A new report in this issue of the European Journal of Immunology advances this notion by showing that CD8(+) T cells lacking the IL-21 receptor phenocopy those primed in the absence of CD4(+) T cells (the so-called "helpless" CD8(+) T cells) in their induction of the pro-apoptotic factor TRAIL. This finding helps to define the role of IL-21 in the CD8 response, and raises new questions relevant for achieving a broader understanding of this multifunctional cytokine.     

Enhanced murine CD4+ T cell responses induced by the CD2 ligand CD48

The physiological functions of murine CD2 and its ligand CD48 are uncertain. We have examined the role of the CD2-CD48 interaction in murine T cell activation using a series of Chinese hamster ovary (CHO) cell transfectants. CHO cells expressing I-A^d together with CD48 induced more potent activation of OVA-specific, I-A^d -restricted DO11.10-transgenic T cells than CHO cells expressing I-A^d alone. CD48 augmented proliferation and IL-2 production in response to antigen. The enhancing effect of CD48 was of the same magnitude as that seen for CD80 (B7-1). Conjugate assays revealed the ability of CD48 to increase adhesion between T cells and CHO transfectants. The enhancing effects of CD48 on T cell-antigen-presenting cell adhesion and T cell activation were inhibited by anti-CD2 monoclonal antibody. This report provides the first evidence that the CD2 ligand CD48 contributes to the interactions of murine CD4⁺ T cells with antigen-presenting cells.     

The CD2 and CD28 adhesion molecules induce long-term autocrine proliferation of CD4+ T cells

In vitro human T lymphocyte activation requires two-signal triggering delivered by lectins, phorbol esters or antibodies directed against surface molecules. Stimulation of adhesion molecules by CD2 and/or CD28 antibodies defines alternative activation pathways. Activation by CD2 + CD28 monoclonal antibodies induces high-level, long-lasting and monocyte-independent proliferation of highly purified T cells. Limiting dilution cultures showed that CD28 in association with CD2 or CD3, without addition of exogenous cytokines, induced single-cell proliferation. CD2 + CD28 stimulation induced long-term interleukin (IL)-2-dependent autocrine proliferation of CD4⁺ T cell clones. We tried to elucidate this long-term proliferation by evaluating cytokine secretion and cytokine dependency. CD28 associated to CD3 or CD2 induced high levels of IL-2, tumor necrosis factor (TNF) and IL-4 secretion for 10 days, in contrast to CD3 alone which induced only TNF secretion. Cytokines of the monocytic lineage were also secreted, such as colony-stimulating factor-1, granulocyte macrophage colony-stimulating factor or IL-1, the latter being more specific of CD2 + CD28 activation. Blocking antibodies confirmed the crucial role of IL-2 in CD2 + CD28 activation. Anti-IL-4, anti-IL-7 receptor or anti-TNF antibodies had no effect on proliferation. Stimulation with CD2 + CD28 induced long-term autocrine (at least for IL-2) proliferation for CD4⁺ T cells, with no evidence for the implication of another cytokine among those tested other than IL-2. This represents a model for long-term autocrine growth for non-leukemic cells.     

Impaired interleukin-2 synthesis and T cell proliferation following antibody-mediated CD3 and CD2 or CD28 cross-linking in trans: evidence that T cell activation requires the engagement of costimulatory molecules within the immunological synapse

Although the T cell costimulatory molecules CD2 and CD28 are enriched within the immunological synapse (IS), it has been suggested that costimulatory molecules need not be localized to the contact site between a T cell and an antigen-presenting cell (APC) in order to costimulate T cell activation. To determine whether CD2 or CD28 engagement outside of the IS is sufficient to costimulate T cell activation, we compared mouse T cell responses to anti-CD3 and anti-CD2 monoclonal antibodies (mAbs) or anti-CD3 and anti-CD28 mAbs immobilized on the same, i.e., in cis, or on different, i.e., in trans, 10 micron polystyrene microspheres. In comparison to T cells that were stimulated with co-immobilized anti-CD3 and anti-CD2 or anti-CD28 mAbs, DNA synthesis, interleukin (IL)-2 production, and cellular proliferation were all severely impaired following T cell stimulation with anti-CD3 and anti-CD2 mAbs or anti-CD3 and anti-CD28 mAbs on different microspheres. Deficient cellular proliferation and IL-2 synthesis by T cells that experienced CD3 and CD2 or CD28 cross-linking in trans provides evidence that costimulatory molecules must function in the context of the IS for optimal T cell activation.     

A novel peripheral CD4+CD8+ T cell population: Inheritance of CD8α expression on CD4+ T cells

In this study we show the inheritance of a CD4⁺CD8⁺ peripheral T cell population in the H.B15 chicken strain. A large proportion of αβ T cells in peripheral blood (20–40%), spleen (10–20%) and intestinal epithelium (5–10%) co-express CD4 and CD8α, but not CD8β. CD4⁺ CD8αα cells are functionally normal T cells, since they proliferate in response to mitogens and signals delivered via the αβT cell receptor as well as via the CD28 co-receptor. These cells induce in vivo a graft versus host-reaction, providing further evidence for their function as CD4⁺ T cells. The CD4⁺CD8αα T cell population was found in 75% of the first progeny and in 100% of further progenies, demonstrating that co-expression of CD4 and CD8 on peripheral T cells is an inherited phenomenon. In addition, cross-breeding data suggest a dominant Mendelian form of inheritance. The hereditary expression of CD8α on peripheral CD4⁺ T cells in chicken provides a unique model in which to study the regulation of CD4 and CD8 expression.     

The role of TCR stimulation and TGF-beta in controlling the expression of CD94/NKG2A receptors on CD8 T cells

Following antigen recognition, murine CD8 T cells express CD94/NKG2A receptors. Our results show that this up-regulation occurs rapidly in vitro and is accompanied by an approximately 8-fold increase in CD94 and approximately 125-fold increase in NKG2A mRNA. In contrast, only a twofold increase in NKG2C mRNA is noted. The addition of TGF-beta, but not IL-10, IL-12 or IL-15, leads to a further increase in cell membrane expression of these receptors, as well as a approximately 6-fold increase in mRNA for both chains. TGF-beta also increases CD94/NKG2A expression on memory CD8 T cells that are re-exposed to antigen. The effect of TGF-beta on increasing CD94/NKG2A expression on both naive and memory CD8 T cells occurs only when there is a concurrent stimulation through the TCR. In contrast, TGF-beta does not increase expression of CD94/NKG2A on resting or activated NK cells. We also show by using purified CD8 T cells, that TGF-beta acts directly on these cells. These results implicate a role for both antigen and TGF-beta in increasing expression of inhibitory CD94/NKG2A receptors on CD8 T cells.