Role of activated T lymphocytes in mycosis fungoides

A patient with mycosis fungoides was treated effectively with the immunosuppressant cyclosporine A. Excretion of urinary neopterin, a marker of activation of the cellular immune system, fell immediately at the start of therapy. This result argues in support of a central role of activated T lymphocytes in this disease as has already been proposed by other authors.     

Modulation of E-receptor expression on activated T lymphocytes

Our study indicated that the newly synthesized E-receptor, as measured with 125I-labeled monoclonal anti-E receptor antibody, on activated T lymphocytes were responsible for forming stable E-rosettes at 37 degrees C. Maximum induction of new E-receptor expression required at least 50 hr of culture with polyclonal T-cell activators, phytohemagglutinin, or phorbol myristate acetate. Polyclonal B-cell activator, lipopolysaccharide were not able to induce new E-receptor expression on the surface of T lymphocytes. The expression of the new E-receptor paralleled with the induction of Tac antigen expression. Interleukins 1 and 2 or Interferon-gamma were not able to initiate the induction of new E-receptors. However, a neuropeptide, endorphin exhibited biphasic effect on modulating the E-receptor expression, in the absence of polyclonal activators. As is the case with Tac antigen expression, induction of new E-receptor antigen may be a marker for activated T lymphocytes.     

激活的人外周T淋巴细胞表达水通道蛋白AQP3

目的:探讨水通道蛋白(Aquaporin,AQP)在人外周T淋巴细胞的表达和生理学意义.方法:利用逆转录PCR和免疫印迹技术检测AQP0～9 mRNA和蛋白在静止的和经活化的T淋巴细胞的表达.结果:静止的淋巴细胞无AQP0-9表达,而活化的T淋巴细胞表达AQP3 mRNA和蛋白.结论:T淋巴细胞激活过程可能需要AQP3转运水和甘油的功能.     

Antibody blocking of MHC II on human activated regulatory T cells abrogates their suppressive potential

Natural regulatory CD4(+)CD25(+)Foxp3(+) T cells control peripheral immune responses. Freshly isolated regulatory T-cell populations are regarded as being unable to suppress the proliferation of strongly stimulated effector T cells. We now provide evidence that it is not the strength of the proliferative signal to effector T cells but activation and accessibility of regulatory T cells that determine whether suppression may occur. Human regulatory T cells were initially cocultured with allogeneic monocyte-derived dendritic cells for a short time and were then rendered accessible for effector T cells by removal of the dendritic cells. That way activated regulatory T cells effectively suppressed the proliferation of autologous effector T cells which was strongly driven by cell-sized Dynabeads coated with CD3/CD28 antibodies. Although regulatory T cells are known to display MHC II molecules and to upregulate their expression along with activation, a role of MHC II molecules in forming the contact to effector T cells was not yet envisaged. However, blocking of MHC II on activated regulatory T cells abrogated their suppressive potential. It should not be excluded that self-MHC molecules on physically accessible activated regulatory T cells arrange the contact to effector T cells.     

Death and destruction of activated T lymphocytes

The massive clonal expansion that occurs during an antigen-specific immune response results in the flooding of immune organs with activated T lymphocytes. At the end of a specific response, the vast majority of these activated T cells are cleared from the immune system. The T cells receive signals through specific death receptors that are expressed as a result of activation. Death receptors transmit their apoptotic signals through the activation of caspases. Function of the death receptors is intimately linked to cell-cycle control, and many cell-cycle control proteins are caspase substrates. Among CD8⁺ T cells, apoptotic death occurs at a specific site, the sinusoids of the liver. The liver appears to contain a mechanism for the trapping and killing of activated T cells, rendering it an immunologically privileged site.     

Role of hematopoietic precursor cells in the restoration of hematopoiesis after treatment with cytostatics

Research Institute of Pharmacology, Tomsk Research Center, Academy of Medical Sciences of the USSR, Tomsk. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 1, pp. 50–51, January, 1992.     

ConA激活的小鼠T细胞CD69表达动力学的体内外研究

目的 为明确ＣＤ６９体内外表达动力学并进一步探讨其作用。方法 ＣｏｎＡ体内外刺激小鼠Ｔ细胞后,选取不同时间点,流式细胞仪观察Ｔ细胞ＣＥ６９表达率。结果ＣｏｎＡ刺激后２ｈＣＤ６９即有明显表达,６～８ｈ达到峰值,ＣＤ８＾＝与ＣＤ８＾＋Ｔ细胞相比无明显差异。体外条件对ＣＤ６９的表达有显著的影响。结论 结果提示ＣＤ８＾－和ＣＤ８＾＋Ｔ细胞的活化均需要ＣＤ６９的参与,Ｔ细胞可能在活化早期一过性高表达ＣＤ６９     

Detection of activated T lymphocytes in the human atherosclerotic plaque

It was recently shown that the human atherosclerotic plaque contains significant amounts of T lymphocytes, and also that smooth muscle cells in these plaques express class II MHC (Ia) antigens. These antigens are not normally present on smooth muscle cells but are inducible by interferon-gamma, a secretory product of activated T cells. Therefore, T cell activation in the plaque was analyzed by immunofluorescent detection of activation markers on T cells isolated from the plaques and in cryostat sections of carotid endarterectomy specimens. Of cells isolated from the plaque, 5% exhibited the E rosettes characteristic of T cells. One third of these cells expressed HLA-DR and VLA-1 (very late activation antigen-1), which in T cells are synthesized only in the activated state. T cells were also identified in sections using immunofluorescent detection of the T cell-specific surface protein, CD3 (Leu-4), with rhodamine labeled second-step antibodies. The frequency of activated T cells was then determined by staining the same, or serial, sections with antibodies to HLA-DR or to the interleukin-2 receptor, followed by biotin-avidin-FITC detection. Of the T cells in the plaque, 34% and 6%, respectively, expressed these cell surface proteins. Taken together, these results indicated that a substantial proportion of the T cells in atherosclerotic plaque are in an activated state. The activation pattern, with a high frequency of HLA-DR and VLA-1 expression and a much lower frequency of interleukin-2 receptor expression, was similar to that reported to occur in chronic inflammatory conditions. Interferon-gamma could be detected in and around some of the lymphocytes, suggesting that paracrine secretion of this lymphokine may occur in the plaque. T cells may be activated locally, presumably by antigen(s) presented in the context of class II MHC expressing smooth muscle cells and/or macrophages, in the atherosclerotic lesion. Such activated T cells may in turn modulate the functions of other cells in the plaque.     

异黄酮Genistein对T细胞体外活化CD69表达的影响

目的 :研究异黄酮Genistein对T淋巴细胞活化的影响 ,探讨将其发展为免疫干预药物的可能性。方法 :应用荧光标记的单克隆抗体和流式细胞技术 ,在全血培养体系中于 2h和 6h时间点检测分别经 10 ,5 0或 10 0 μmol L浓度Genistein预培养的 ,PHA或PDB诱导活化的T细胞的CD6 9表达百分率。结果 :培养 2h后 ,Genistein对PHA活化组的抑制作用要强于PDB活化组 ,P <0 0 5 ;培养 6h后 ,Genistein对PHA活化组的抑制作用同样强于PDB活化组 ,P <0 0 5 ,但较之 2h时间点均有所降低 ;无论PHA活化组或PDB活化组 ,Genistein对T细胞CD6 9表达率的抑制效应均随作用浓度的升高而增强。结论 :Genistein对PHA和PDB诱导活化的T细胞的CD6 9表达率均有明显的抑制作用 ,这种抑制作用存在浓度依赖关系。Genistein有潜力发展成一种免疫干预药物。     

Apoptotic cells actively inhibit the expression of CD69 on Con A activated T lymphocytes

Although apoptosis is commonly viewed as a silent cell death without damage to adjacent tissues, the effect of apoptosis on immunity has been unclear. We have investigated the influence of apoptotic cells on T-cell activation. The K562 or HL-60 human leukemia cell lines that had been induced apoptosis by FTY720 or cycloheximide (CHX) were added into the culture of mouse spleen cells stimulated with Con A. Six to 20 h later, the expression of CD69, an early T-cell activation antigen, was detected using flowcytometry. Living cells and necrotic cells served as control groups. Apoptotic K562 or HL-60 cells induced by either FTY720 or CHX unanimously inhibited CD69 expression on the CD3+ mouse T cells while living and necrotic cells did not. The inhibition was proportional to the number of apoptotic cells and was different in the T-cell subsets, showing a rapid and transient inhibition on the CD3+CD8+ T-cell activation but with a slow and continuous inhibition on CD3+CD8- T-cell activation. In conclusion, the apoptotic cells actively inhibit a T-cell activation that is independent of the cell lines or the apoptotic inducers, indicating that the apoptotic cells dominantly regulate T-cell immunity.     

Inorganic arsenic alters expression of immune and stress response genes in activated primary human T lymphocytes

Inorganic arsenic, a carcinogenic environmental contaminant, exerts immunosuppressive effects on human T lymphocytes. In particular, interleukin-2 (IL2) secretion and T cell proliferation are reduced when peripheral blood mononuclear cells (PBMC) from individuals chronically exposed to arsenic are stimulated ex vivo with lectins such as phytohemaglutinin (PHA). However, it is not clear whether the metalloid directly acts on T cells or blocks monocyte-dependent accessory signals activated by PHA. We report that in vitro pre-treatment of PBMC with sodium arsenite (NaAs) reduces IL2 secretion and T cell proliferation induced by PHA, but does not prevent expression of monocyte-derived cytokines (IL1, IL6, TNFα) functioning as lymphocyte-activating factors. In addition, we found that NaAs delays induction of IL2 and IL2 receptor α chain (IL2RA) mRNA levels in human primary isolated T cells activated by PHA. Kinetic analysis showed that NaAs pre-treatment first inhibits, but thereafter markedly increases, induction of IL2 and IL2RA mRNA when T cells are stimulated with PHA for 8 h and 72 h, respectively. We conducted whole genome microarray-based analysis of gene expression in primary T cell cultures derived from independent donors. NaAs systematically and significantly up-regulated a set of 35 genes, including several immune and stress genes, such as IL13, granulocyte-macrophage colony stimulating factor, lymphotoxin α and heme oxygenase-1 (HO-1). Up-regulation of HO-1, a stress and immunosuppressive protein, was rapidly detectable, both in T cells and in PBMC treated with NaAs. Inhibition of the immunosuppressive activity of HO-1 in PBMC however failed to prevent NaAs-dependent inhibition of T cell proliferation induced by PHA. Our findings demonstrate that, at least in vitro, inorganic arsenic acts directly on human T cells and impairs their activity, probably independently of HO-1 expression and monocyte-related accessory signals.     

Role of humoral factors in regulation of hematopoiesis during stress

Research Institute of Pharmacology, Tomsk Scientific Center, Academy of Medical Sciences of the USSR. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 7, pp. 15–18, July, 1991.     

T cell suppression in vitro. II. Nature of specific suppressive factor

The mechanism of specific T cell suppression in vitro was investigated. It was found that suppression of hapten-reactive B cells only occurred in the presence of hapten linked to the carrier to which the T cells were reacting. Thus, there was the same requirement for linked recognition in T cell suppression as was previously described in cooperation. The nature of the suppressive factor was investigated, and like the cooperating factor, it was found to have specificity for the immunizing carrier protein and to be fully absorbed by peritoneal macrophages. The ratio of helper to suppressor activity obtained from activated T cells did not change between 4 and 8 days after injection of antigen and thymocytes. Both activities were absorbed by Sepharose beads conjugated with polyvalent anti-mouse Ig, anti-? or anti-μ-chain antibody. There was thus a resemblance between the T cell suppressive factor and the immunizing factor, although it is not yet known whether both properties are expressed by one and the same molecule. This must await further biochemical characterization of specific T cell factors.     

孕酮对人T淋巴细胞体外活化CD69表达的作用

目的：探讨孕酮（Ｐｒｏｇｅｓｔｅｒｏｎｅ,Ｐｒｏｇ）及地塞米松（Ｄｅｘａｍｅｔｈａｓｏｎｅ,Ｄｅｘ）对人外周血Ｔ淋巴细胞体外活化ＣＤ６９表达的作用。方法：以女性健康志愿者（１０名）为研究对象,以蛋白激酶Ｃ的刺激剂佛波醇酯（Ｐｈｏｒｂｏｌ ｅｓｔｅｒ,ＰＤＢ）为Ｔ淋巴细胞的活化剂,采用双荧光染色流式细胞技术。检测ＣＤ３＾＋的Ｔ淋巴细胞表达早期活化表面分子ＣＤ６９的百分率,以观察Ｐｒｏｇ、Ｄｅｘ及Ｐｒｏ０ｇ加上Ｄｅｘ对外周血Ｔ淋巴细胞体外活化的作用。结果：在体外培养条件下,无论单独使用Ｐｒｏｇ还是Ｄｅｘ均地强低剂量ＰＤＢ刺激ＣＤ６９的表达。然而,与单独使用Ｐｒｏｇ或Ｄｅｘ的作用相比。Ｐｒｏｇ加上Ｄｅｘ明显减弱低剂量ＰＤＢ的活化ＣＤ６９的表达。结论：同时使用Ｐｒｏｇ与Ｄｅｘ可明显抑制Ｔ淋巴细胞的体外活化,提示在临床上     

PSGL-1-mediated adhesion of human hematopoietic progenitors to P-selectin results in suppression of hematopoiesis.

Cellular interactions are critical for the regulation of hematopoiesis. The sialomucin PSGL-1/CD162 mediates the attachment of mature leukocytes to P-selectin. We now show that PSGL-1 also functions as the sole receptor for P-selectin on primitive human CD34+ hematopoietic progenitor cells (HPC). More importantly, ligation of PSGL-1 by immobilized or soluble ligand or anti-PSGL-1 antibody results in a profound suppression of HPC proliferation stimulated by potent combinations of early acting hematopoietic growth factors. These data demonstrate an unanticipated but extremely marked growth-inhibitory effect of P-selectin on hematopoiesis and provide direct evidence that PSGL-1, in addition to its well-documented role as an adhesion molecule on mature leukocytes, is a potent negative regulator of human hematopoietic progenitors.