香菇多糖对小鼠T淋巴细胞膜上离子通道基因表达的影响

目的:研究香菇多糖对小鼠T淋巴细胞膜上离子通道基因表达的影响。方法:40只KM小鼠随机分为对照(等容生理盐水)组与香菇多糖高、中、低剂量(12.5、2.5、0.5 mg/kg)组,腹腔注射,每天1次,连续30 d。末次给药1 h后处死小鼠,采用实时荧光定量聚合酶链反应(RT-qPCR)法检测小鼠T淋巴细胞内电压门控钾离子通道(KV1.3)、Ca2+激活的钾离子通道(KCa3.1)、阳离子通道(TRPM7)、氯离子通道(Clswell)以及钙离子通道(CRAC)激活的调控元件基质相互作用因子1(STIM1)和组成分子orai1mRNA的表达。结果:与对照组比较,香菇多糖中剂量组小鼠T淋巴细胞KV1.3、KCa3.1、STIM1、orai1、TRPM7、Clswell mRNA表达增强,差异有统计学意义(P<0.05)。结论:香菇多糖可提高小鼠T淋巴细胞增殖及活性,其机制与增强T细胞上的KV1.3、KCa3.1、orai1、STIM1、TRPM7、Clswel mRNA表达有关。     

T 淋巴细胞免疫功能与儿童哮喘

T淋巴细胞的免疫功能越来越受到人们的广泛重视,该淋巴细胞介导人体细胞免疫,在很多疾病的发生发展中发挥重要作用。儿童哮喘与T淋巴细胞免疫功能之间的关系已经受到国内外学者的高度关注。不同种类的T淋巴细胞及其亚群在儿童哮喘中发挥着各自不同的作用,其细胞亚群之间的平衡关系错综复杂,与B淋巴细胞介导的体液免疫关系密切,相互影响。 T淋巴细胞及其相关的细胞因子和炎性介质之间的相互作用,导致了儿童哮喘的发生发展。本文就T淋巴细胞免疫功能与儿童哮发生发展的相关性作一综述。     

伤寒病患者淋巴细胞内腺苷氨酶活性的变化与T淋巴细胞亚群的关系

目的　对 34例伤寒病患者进行了外周血淋巴细胞内腺苷脱氨酶 (LADA)活性和T 淋巴细胞亚群的测定。方法　应用免疫学技术测定外周LADA活性和单克隆抗体技术测定T 淋巴细胞亚群。结果　伤寒病患者外周血LADA活性高于正常人组 (P <0 .0 1) ,外周血淋巴细胞CD4、CD8及CD4/CD8比值差异也有显著性 (P <0 .0 1) ,相关分析显示 :LADA活性与CD4/CD8比值呈高度相关 (P <0 .0 1)。结论　伤寒病患者淋巴细胞内ADA活性升高与T淋巴细胞亚群比例失调相关     

46例新生儿T淋巴细胞及亚群的测定

为了解健康新生儿及某些疾病状况下新生儿的免疫情况，应用人Ｔ细胞单克隆抗体（ＭｃＡｂ）对健康新生儿及早产、窒息、肺炎、皮肤感染等疾病的４６例新生儿进行了Ｔ淋巴细胞及亚群的检测。结果提示各种疾病状况下新生儿的细胞免疫功能均有不同程度的降低，其中尤以早产新生儿的免疫功能低下更为明显。     

恶性血液病患者T淋巴细胞亚群的检测分析

目的探讨恶性血液病患者外周血T淋巴细胞亚群的特征及其临床意义。方法应用流式细胞仪对120例恶性血液病患者（急性白血病、慢性白血病、淋巴瘤、多发性骨髓瘤）及40例正常人外周血T淋巴细胞亚群进行检测,并比较各组的差异。结果恶性血液病组的CD3＋、CD4＋、CD4＋/CD8＋、CD3＋CD16＋CD56＋T淋巴细胞比例低于对照组,CD8＋T淋巴细胞比例高于对照组,差异有统计学意义（P〈0.05）;AL组、CL组、LM组和MM组的CD3＋、CD4＋、CD4＋/CD8＋、CD3＋CD16＋CD56＋T淋巴细胞比例低于对照组,CD8＋T淋巴细胞比例高于对照组,差异有统计学意义（P〈0.05）。结论恶性血液病患者机体免疫功能失衡导致机体免疫力下降,抗肿瘤能力减弱,T淋巴细胞亚群的检测可以为恶性血液病的诊断、治疗及判断预后提供依据。     

20例再生障碍性贫血患者T淋巴细胞及红细胞免疫功能测定

２０例再生障碍性贫血ＣＤ３、ＣＤ４值均比正常对照组降低（Ｐ〈０．０５）、ＣＤ８值比正常对照增高（Ｐ〈０．０５），ＣＤ４／ＣＤ８比值降低、说明Ｔ淋巴细胞免疫功能低下。红细胞Ｃ３ｂ受体粘附率比正常健康人降低，红细胞循环免疫复合物则增高（Ｐ〈０．０１）说明再障患者红细胞免疫功能低下。     

高压氧对严重创伤病人T淋巴细胞Ag-NORs含量的影响

严重创伤可导致机体免疫功能紊乱,尤其是T淋巴细胞免疫功能的改变特别明显.本研究探讨高压氧对严重创伤患者T淋巴细胞核仁形成区嗜银蛋白(Ag-NORs)含量的影响,为临床严重创伤的干预治疗提供新的途径.     

T淋巴细胞相关肿瘤免疫疗法的研究进展

目的:了解T淋巴细胞相关肿瘤免疫疗法的研究进展,以期为肿瘤的免疫治疗提供参考。方法:笔者查阅近年来国内外相关文献,就T淋巴细胞相关肿瘤免疫疗法的研究进行归纳和总结。结果:T淋巴细胞相关肿瘤免疫疗法免疫检查点疗法和嵌合抗原受体T细胞免疫疗法在临床前与临床研究中取得了良好的成效。多个肿瘤免疫治疗药物,尤其是针对细胞毒T淋巴细胞相关抗原4、程序性死亡受体1(PD-1)和PD-1配体这3个靶标的肿瘤免疫治疗药物被各研究机构和医药企业作为研发热点,其中Ipilimumab、Tremelimumab和Nivolumab已被FDA批准用于临床,且疗效显著。肿瘤免疫疗法通过诱导自身免疫系统对抗肿瘤,但多种因素影响T淋巴细胞对肿瘤的识别,造成肿瘤免疫逃逸。结论:肿瘤免疫疗法还存在一定的局限性,但其在肿瘤治疗中是一个非常有前景的研究方向,有望成为攻破肿瘤治疗的有效方法。     

T淋巴细胞与创伤愈合

机体在受到创伤后全身和局部的免疫状态会发生复杂的变化。免疫系统除了在机体防御及炎症反应中起作用，还通过免疫细胞产生多种细胞因子对创伤愈合过程进行调节，并伴随创伤修复的整个过程。T淋巴细胞是参与细胞免疫反应的主要细胞之一，它通过识别抗原并产生各种细胞因子来参与创伤愈合的调控。完整的细胞免疫反应对良好的组织修复是必需的，而各种导致淋巴细胞功能低下的因素会延缓伤口愈合。该文就创伤后T淋巴细胞的变化及其在创伤愈合中的作用等方面作一介绍。     

The action of prostaglandins on ion channels

Prostaglandins, in particular PGE(2) and prostacyclin PGI(2) have diverse biological effects. Most importantly, they are involved in inflammation and pain. Prostaglandins in nano- and micromolar concentrations sensitize nerve cells, i.e. make them more sensitive to electrical or chemical stimuli. Sensitization arises from the effect of prostaglandins on ion channels and occurs both at the peripheral terminal of nociceptors at the site of tissue injury (peripheral sensitization) and at the synapses in the spinal cord (central sensitization). The first step is the binding of prostaglandins to receptors in the cell membrane, mainly EP and IP receptors. The receptors couple via G proteins to enzymes such as adenylate cyclase and phospholipase C (PLC). Activation of adenylate cyclase leads to increase of cAMP and subsequent activation of protein kinase A (PKA) or PKA-independent effects of cAMP, e.g. mediated by Epac (=exchange protein activated by cAMP). Activation of PLC causes increase of inositol phosphates and increase of cytosolic calcium. This article summarizes the effects of PGE(2), PGE(1), PGI2 and its stable analogues on non-selective cation channels and sodium, potassium, calcium and chloride channels. It describes the mechanism responsible for the facilitatory or inhibitory prostaglandin effects on ion channels. Understanding these mechanisms is essential for the development of useful new analgesics.     

Overview of the relationship between structure and functin in ion channels

This review briefly introduces the known classes of ion channels, describes conceptual insights gained from structure-function work, and discusses the limitations of the techniques use. Finally, unresolved issues and promising future directions are highlighted. © 1994 Wiley-Liss, Inc.     

The interaction of mu-opioid receptors with ion channels and G-proteins

The state-of-the-art in investigations of the mu-opioid receptors (ORs) is reviewed. Published information on the interaction between mu-ORs and various G-proteins is summarized and data on the neutral antagonists and inverse agonists of mu-opioid receptor are generalized. The notions about the spontaneous activation of mu-ORs are considered and numerous reports on the interaction between mu-ORs and GIRK, KATP, and Kv channels are analyzed. The role of L, N, and P/Q types of Ca(2+)-channels in mu-OR-mediated intracellular signaling is discussed.     

雷帕霉素对小鼠T淋巴细胞的体外作用

目的 研究雷帕霉素对小鼠T淋巴细胞体外的增殖、白细胞介素2(IL-2)表达及细胞周期的影响.方法 将C57BL/6小鼠脾脏制备成脾单个核细胞,使用免疫磁珠法分选出小鼠T淋巴细胞.T细胞分别加入0、10、20、30和40 ng/ml梯度浓度的雷帕霉素培养液培养72 h后,采用MTT法及ELISA法测定各组细胞的增殖情况及IL-2表达情况;用流式细胞仪测定40 ng/ml雷帕霉素浓度组及对照组(0 ng/ml)细胞周期的变化情况.结果 用雷帕霉素培养液培养细胞时,细胞增殖及IL-2的表达均受到抑制(P＜0.01).随药物浓度增加,细胞增殖及IL-2表达受抑制越明显(P＜0.01);细胞周期分析显示加入雷帕霉素培养的T淋巴细胞与未使用药物刺激者相比,G0G1期细胞的比例升高(P＜0.01),S期降低(P＜0.01).结论 在体外雷帕霉素对小鼠T细胞的增殖、IL-2的表达起抑制作用,且随浓度增加,抑制作用增强;雷帕霉素将小鼠T细胞抑制在G0G1期.     

Dopamine receptor agonists differ in their actions on cardiac ion channels

Four dopamine receptor agonists used for the treatment of Parkinson's disease (apomorphine, pergolide, ropinirole and sumanirole) were evaluated for the ability to block human ether-a-go-go related gene (hERG) K(+) channels and to modify the duration of canine Purkinje fiber action potentials. Apomorphine, pergolide and ropinirole blocked the hERG-mediated currents with IC(50) values of 2.4, 0.12 and 1.2 microM, respectively. When evaluated in an action potential duration assay, pergolide significantly shortened action potential duration at 90% repolarization (APD(90)) whereas apomorphine and ropinirole significantly prolonged repolarization. Sumanirole only partially blocked hERG K(+) channels at the highest tested concentration (10 microM) and did not modify action potential duration over the tested concentration range (0.65-65 microM). Taken together, these data provide evidence that dopamine receptor agonists developed for the treatment of Parkinson's disease differentially influence hERG K(+) channel function and cardiac action potential duration.     

Anuroctoxin, a new scorpion toxin of the alpha-KTx 6 subfamily, is highly selective for Kv1.3 over IKCa1 ion channels of human T lymphocytes

The physiological function of T lymphocytes can be modulated selectively by peptide toxins acting on Kv1.3 K(+) channels. Because Kv1.3-specific peptide toxins are considered to have a significant therapeutic potential in the treatment of autoimmune diseases, the discovery of new toxins is highly motivated. Through chromatographic procedures and electrophysiological assays, using patch-clamp methodology, the isolation of a novel peptide named anuroctoxin was accomplished using the venom of the Mexican scorpion Anuroctonus phaiodactylus. It has 35 amino acid residues with a molecular weight of 4082.8, tightly bound by four disulfide bridges whose complete covalent structure was determined. It has a pyroglutamic acid at the N-terminal region and an amidated C-terminal residue. Sequence comparison and phylogenetic clustering analysis classifies anuroctoxin into subfamily 6 of the alpha-KTx scorpion toxins (systematic name, alpha-KTx 6.12). Patch-clamp experiments show that anuroctoxin is a high-affinity blocker of Kv1.3 channels of human T lymphocytes with a K(d) of 0.73 nM, and it does not block the Ca(2+)-activated IKCa1 K(+) channels. These two channels play different but important roles in T-lymphocyte activation. Furthermore, the toxin practically does not inhibit Shaker IR, mKv1.1, and rKv2.1 channels, whereas the affinity of anuroctoxin for hKv1.2 is almost an order of magnitude smaller than for Kv1.3. The pharmacological profile and the selectivity of this new toxin for Kv1.3 over IKCa1 may provide an important tool for the modulation of the immune system, especially in cases in which selective inhibition of Kv1.3 is required.     

猴耳环的化学成分及其对T淋巴细胞增殖的影响

目的研究猴耳环Pithecellobium clypearia Benth枝叶的化学成分及其免疫活性。方法采用多种色谱学方法进行分离纯化,利用波谱学方法进行结构鉴定;并通过ConA诱导的T淋巴细胞增殖试验考察各化合物的免疫活性。结果从中分离并鉴定了8个化合物,分别为（-）-表没食子儿茶素（1）,（-）-5,7,3′,4′,5′-五羟基黄烷（2）,（-）-表没食子儿茶素-7-没食子酸酯（3）,（-）-5,3′,4′,5′-四羟基黄烷-7-没食子酸酯（4）,槲皮素-3-O-α-L-吡喃鼠李糖苷（5）,杨梅树皮素-3-O-α-L-吡喃鼠李糖苷（6）,没食子酸（7）,没食子酸乙酯（8）。结论化合物3和8为首次从该属植物中分离得到,化合物1为首次从该种植物中分离得到;化合物3能显著抑制ConA诱导的T淋巴细胞增殖,其IC50为4.4μmol·L^-1。     

Modulation of voltage-gated potassium channels in human T lymphocytes by extracellular glutamate

Glutamate is present in the plasma under tightly regulated concentrations. However, under conditions of immune deficiency, such as AIDS and malignancy, its plasma levels are highly elevated. In vitro, glutamate interacts with T lymphocytes, affecting mitogen-induced calcium responses, whereas at high doses, it impairs T lymphocyte proliferation, a process strongly dependent on the activity of voltage-gated potassium channels. In this study, we demonstrate novel dose-related effects of the endogenous ligand glutamate and its metabotropic and non-N-methyl-D-aspartic acid receptor agonists on the electrophysiological properties of native Kv1.3 channels of human T lymphocytes. Glutamate, at concentrations within normal plasma levels, positively modulates Kv1.3 channel gating, causing currents to activate faster and at significantly more hyperpolarized potentials, hence rendering the T lymphocyte readily responsive to immune stimuli. This effect is maximal at 1 microM Glu and is fully mimicked by a 100 microM concentration of the metabotropic receptor agonist trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid. Most importantly, Glu, at concentrations > or =100 microM, which in vitro produce suppression of mitogen-induced proliferation, significantly decreases whole-cell potassium currents by increasing current and steady-state inactivation. This effect saturates at 1000 microM and seems to result from the subsequent activation of low-affinity metabotropic Glu receptors, as suggested by specific agonist data. Therefore, the antiproliferative effects of high glutamate may, at least in part, result from its inhibitory effect on the potassium current, suggesting an in vivo immunosuppressive role of elevated plasma glutamate.     

Quercetin inhibition of the induction and function of cytotoxic T lymphocytes

Quercetin is a naturally occurring flavonoid, chemically related to cromolyn. Quercetin has been shown to inhibit antigen- and mitogen-induced histamine release from rat mast cells and basophils of subjects with hay fever, to increase cyclic adenosine monophosphate (AMP) in Ehrlich ascites tumor cells and to inhibit phosphodiesterase and certain adenosine triphosphatase (ATPase) systems. We have studied the effect of quercetin on mouse T cell responses. When 5 x 10(-6) to 5 x 10(-5) M quercetin is present throughout either allogeneic mixed leukocyte culture (MLC) or cytotoxic T lymphocyte (CTL) assay culture, inhibition of in vitro CTL generation or effector function results, respectively (inhibition is 75-100% at 2 x 10(-5) M and 100% at 5 x 10(-5) M). Quercetin also inhibits concanavalin A-induced DNA synthesis. Addition of Cu2+ strongly blocks the effects of quercetin in all systems tested, in a concentration dependent fashion, while Mg2+ and Ca2+ have little or no effect and Mn2+ and Co2+ have a significant but slight blocking effect on quercetin-mediated inhibition of both CTL generation and function. In kinetic studies, evidence was obtained for the existence of a major quercetin-sensitive step in CTL induction, between 3 and 24 hr of the MLC.     

Endogenous lipid-derived ligands for sensory TRP ion channels and their pain modulation

Environmental or internal noxious stimuli excite the primary sensory nerves in our body. The sensory nerves relay these signals by electrical discharges to the brain, leading to pain perception. Six transient receptor potential (TRP) ion channels are expressed in the sensory nerve terminals and play a crucial role in sensing diverse noxious stimuli. Cation influx through activated TRP ion channels depolarizes the plasma membrane, resulting in neuronal excitation and pain. Natural and synthetic compounds have been found to act on these sensory TRP channels to alter the nociception. Evidence is growing that lipidergic substances are also cable of modifying TRP ion channel activity by direct binding. Here, we focus on endogenously generated lipids that modulate the sensory TRP activities. Unsaturated fatty acids or their metabolites via lipoxygenase, cyclooxygenase or epoxygenase are able to modulate (activate, inhibit or potentiate) the function of specific TRPs. Isoprene lipids, diacylglycerol, resolvin, and lysophospholipids also show distinct activities on sensory TRP channels. Outcomes caused by the interactions between sensory TRPs and lipid ligands are also discussed. The knowledge we collected here implicates that information on lipidergic ligands may contribute to our understanding of peripheral pain mechanism and provide an opportunity to design novel therapeutic strategies.