scholarly journals Voltage-gated potassium channels are required for human T lymphocyte activation.

1984 ◽  
Vol 160 (2) ◽  
pp. 369-385 ◽  
Author(s):  
K G Chandy ◽  
T E DeCoursey ◽  
M D Cahalan ◽  
C McLaughlin ◽  
S Gupta
Keyword(s):  
Protein Synthesis ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
K Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Two Dimensional Gel Electrophoresis ◽  
K Channels ◽  
T Lymphocyte Activation

The calcium channel blockers, verapamil and diltiazem, inhibit phytohemagglutinin (PHA)-induced mitogenesis at concentrations that block the T lymphocyte K channel currents. K channel blockers also inhibit the allogeneic mixed lymphocyte response in a dose-dependent manner with the same potency sequence as for block of K currents. K channel blockers inhibit PHA-stimulated mitogenesis only if added during the first 20-30 h after PHA addition, but not later, indicating a requirement for functional K channels during this period. We investigated the effect of K channel blockers on various aspects of protein synthesis for two reasons: first, protein synthesis appears to be necessary for the events leading to DNA synthesis, and second, the increase in the protein synthetic rate commences during the first 24-48 h after PHA addition. PHA-induced total protein synthesis was reduced to the level in unstimulated T lymphocytes by K channel blockers in a dose-dependent manner with the same potency sequence as for the block of K currents and inhibition of [3H]thymidine incorporation. Two-dimensional gel electrophoresis demonstrated that although the synthesis of the majority of proteins was reduced by K channel blockers to the level in unstimulated T cells, some proteins continued to be synthesized at an enhanced rate compared with resting cells. Two proteins, S and T, detected by two-dimensional gel electrophoresis in unstimulated T lymphocytes, appeared to be reduced in intensity in gels of PHA-treated T lymphocytes, in contrast to the increased synthesis of the remaining proteins. 4-Aminopyridine (4-AP), at concentrations that inhibit protein synthesis, prevented the apparent PHA-induced reduction of proteins S and T. These proteins may play a role in maintaining the T lymphocyte in a resting state and may be related to the translation inhibitory factors reported to be present at a higher specific activity in quiescent T lymphocytes than in PHA-activated T cells. The expression of the IL-2 receptor (Tac) during T lymphocyte activation was not altered by K channel blockers, whereas the production of interleukin 2 (IL-2) was reduced to the level in unstimulated T lymphocytes. Exogenous IL-2 partially relieved the inhibition of mitogenesis by low, but not by high, concentrations of 4-AP. These experiments clarify the role of K channels in T lymphocyte activation and suggest that functional K channels are required either for protein synthesis or for events leading to protein synthesis.

scholarly journals Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis

2011 ◽  
Vol 19 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Alexandre S. de Almeida ◽  
Christina T. Fiske ◽  
Timothy R. Sterling ◽  
Spyros A. Kalams
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Treg Cell ◽  
T Lymphocyte ◽  
Extrapulmonary Tuberculosis ◽  
Lymphocyte Activation ◽  
Content Type ◽  
T Lymphocyte Activation ◽  
Previously Treated

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.

Rat Prl and TSH secretion are regulated differently by K(+)-channel blockers

1994 ◽  
Vol 266 (1) ◽  
pp. E39-E43 ◽  
Author(s):  
X. Wang ◽  
T. Inukai ◽  
M. A. Greer ◽  
S. E. Greer
Keyword(s):  
Channel Blocker ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Thyroid Stimulating Hormone ◽  
K Channel ◽  
Channel Blockers ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
K Channels ◽  
Tsh Secretion

All four different K(+)-channel blockers [tetraethylammonium (TEA), a nonselective K(+)-channel blocker; tolbutamide, an ATP-sensitive K(+)-channel blocker; quinine and 4-aminopyridine, both primarily voltage-dependent K(+)-channel blockers] stimulated prolactin (Prl) secretion by acutely dispersed anterior pituitary cells but had no effect on thyroid-stimulating hormone (TSH) secretion. TEA stimulated Prl secretion in a dose-dependent manner between 1 microM and 20 mM, but even as high as 20 mM, TEA did not induce TSH secretion. Valinomycin (2 microM), a K+ ionophore, inhibited both basal and TEA-induced Prl secretion. TEA-stimulated Prl secretion was abolished by using a Ca(2+)-depleted medium or adding 10 microM dopamine. TEA did not reverse the inhibitory effect of dopamine on thyrotropin-releasing hormone-induced Prl secretion. Our data indicate that K+ channels may play a role in the secretion of adenohypophysial hormones that is idiosyncratic for each hormone. Differences in the role of K+ channels may reflect differences between the various pituitary cell types in plasma membrane ion channel composition, membrane potential, or the mechanism of exocytosis.

scholarly journals Immune cell populations in cutaneous delayed-type hypersensitivity.

1983 ◽  
Vol 158 (4) ◽  
pp. 1227-1242 ◽  
Author(s):  
J L Platt ◽  
B W Grant ◽  
A A Eddy ◽  
A F Michael
Keyword(s):  
Monoclonal Antibodies ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Lymphocyte Activation ◽  
Delayed Type Hypersensitivity ◽  
Cell Populations ◽  
T Lymphocyte Activation ◽  
Cutaneous Response ◽  
Leu 7

Delayed-type hypersensitivity (DTH) is a prototypic T lymphocyte-mediated response to antigenic challenge. In this study, mononuclear cells infiltrating the skin during cutaneous response to tuberculin in presensitized human subjects (responders) and nonimmune controls were identified using monoclonal antibodies by indirect immunofluorescence. In both responders and controls the infiltrate consisted mainly of T lymphocytes (T11+ and OKT3+) and monocytes (OKM1+, 63D3+, Mo2+) which initially accumulated in proximity to small blood vessels and later infiltrated the interstitial dermis and epidermis. More T lymphocytes reacted with OKT4 than with OKT8. 6 h after tuberculin the ratio of OKT4/OKT8 in tissue from responders exceeded that in blood, whereas in tissues studied at 15-48 h and in all control tissues those ratios in blood and tissue were similar. Evidence of T lymphocyte activation was sought using monoclonal antibodies anti-Tac, OKT9, and OKT10. In responders but not in controls the proportion of infiltrating cells reactive with these antibodies increased during the course of DTH. The presence of activated T lymphocytes in tissue was not associated with a comparable increase in peripheral blood cell populations identified by anti-Tac and OKT10. Studies using anti-B1, Leu-7, and anti-IgD/IgM revealed comparatively few reactive cells. Dual-labeling studies demonstrated that most Leu-7--reactive cells also bound T11 while fewer bound OKM1 or OKT8 and that cells reactive with OKIa1 and T11 constituted largely nonoverlapping populations. Specific patterns of reactivity were not observed when tissues were stained with anti-human C3, or poly C9-MA, a monoclonal antibody reactive with a neoantigen on polymerized C9 of the membrane attack complex of complement. The number of epidermal Langerhans cells identified by OKT6 was similar in responders and controls. Thus, the cutaneous response to tuberculin in sensitized individuals is characterized by early enrichment of the OKT4 subpopulation of T lymphocytes in tissue infiltrates and subsequent (15-48 h) evidence of T lymphocyte activation.

scholarly journals Hydrogen peroxide promotes the activation of preeclampsia peripheral T cells

2018 ◽  
Vol 24 (4) ◽  
pp. 203-209 ◽  
Author(s):  
Jingzhu Lv ◽  
Xiaojie Zhang ◽  
Caizhi Wang ◽  
Hongtao Wang ◽  
Ting Wang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Immune Activation ◽  
Lymphocyte Activation ◽  
Neutrophil Granulocytes ◽  
T Lymphocyte Activation ◽  
Hla Dr ◽  
Intracellular Ros ◽  
Oxidative Stress Status ◽  
High Oxidative Stress

Preeclampsia (PE) is a pregnancy disorder with a high mortality rate. Patients with PE exhibit systemic high oxidative stress status and inflammatory immune activation. This study aims to define the role of H2O2 in the activation of neutrophils and T lymphocytes in PE patients. CD3+/HLA-DR+ cells in blood from PE patients are remarkably increased compared with those of normal non-pregnancies or normal pregnancies, while the percentage of CD3+/CD62L+ cells is significantly reduced in PE patients compared to normal pregnancies. Furthermore, CD62L levels in granulocytes of periphery blood of PE patients are significantly higher than non-pregnancies, but significantly lower than normal pregnancies. To characterize the effects of intracellular reactive oxygen species (ROS) on T lymphocyte activation in PE patients, PBMCs from normal pregnancies were challenged with H2O2, and intracellular ROS levels in neutrophil granulocytes, as well as T cell surface marker levels, have been determined. We confirm that H2O2 exposure increases intracellular ROS levels in neutrophil granulocytes, and increases the proportion of CD3+/HLA-DR+ cells, but does not alter the percentage of CD3+/CD62L+ cells in PBMCs. Our study has confirmed dysregulated CD3+/HLA-DR+ and CD3+/CD62L+ T lymphocytes in PE patient peripheral blood, and the dysregulative effects of H2O2 on T lymphocyte activation, suggesting a novel mechanism of immune activation in PE.

Effect of dexamethasone on expression of adhesion molecules on CD4+ lymphocytes

1996 ◽  
Vol 271 (1) ◽  
pp. L79-L84
Author(s):  
J. M. Hughes ◽  
W. A. Sewell ◽  
J. L. Black ◽  
C. L. Armour
Keyword(s):  
T Lymphocytes ◽  
Cell Surface ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cell Surface Markers ◽  
T Lymphocyte Activation ◽  
Beta 1 Integrin ◽  
Memory T Lymphocytes

Despite the widespread use of corticosteroids in asthma therapy, little is known of the effects of corticosteroids on cell surface markers involved in T lymphocyte activation and adhesion. We used flow cytometry to analyze the effects of 1, 10, and 100 nM dexamethasone on expression of markers on resting and phytohemagglutinin (PHA)-stimulated peripheral blood CD4+ T lymphocytes. Expression of the leukocyte common antigen CD45 was significantly (P = 0.016, n = 3) increased from an average mean fluorescence intensity of 215.8 [95% confidence intervals (CI): 100.5, 463.5] on cells from unstimulated cultures to 334.2 (CI: 167.9, 663.7) on cells from PHA-stimulated cultures after 70-h incubation. At the same time, the percentage of cells also expressing the CD45RO isoform, a marker of memory T lymphocytes, increased significantly (P = 0.0006, n = 3) from 54.4 +/- 1.3% (unstimulated) to 92.8 +/- 0.6% (stimulated). Dexamethasone had no significant effect on expression of CD45 or CD45RO, including the observed changes. Dexamethasone also did not affect expression of the beta 1-integrin VLA-4. These results suggest that corticosteroids do not modulate the cell surface expression of these molecules involved in CD4+ T lymphocyte activation, adhesion, and recirculation.

scholarly journals c-myb protein expression is a late event during T-lymphocyte activation.

1987 ◽  
Vol 7 (9) ◽  
pp. 3358-3360 ◽  
Author(s):  
J S Lipsick ◽  
W J Boyle
Keyword(s):  
Cell Cycle ◽  
T Lymphocytes ◽  
Protein Expression ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
S Phase ◽  
Human T Lymphocytes ◽  
T Lymphocyte Activation ◽  
Late Event ◽  
Myb Protein

The expression of p80c-myb was examined during the activation of resting human T lymphocytes. Before activation, no detectable p80c-myb was present. Synthesis of p80c-myb was observed only after initiation of the S phase of the cell cycle.

TEA inhibits ACh-induced EDRF release: endothelial Ca(2+)-dependent K+ channels contribute to vascular tone

1994 ◽  
Vol 267 (3) ◽  
pp. H1135-H1141 ◽  
Author(s):  
E. Demirel ◽  
J. Rusko ◽  
R. E. Laskey ◽  
D. J. Adams ◽  
C. van Breemen
Keyword(s):  
Endothelial Cells ◽  
Patch Clamp ◽  
Outward Current ◽  
Rabbit Aorta ◽  
K Channel ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
K Channels ◽  
Donor Segment

The effects of K(+)-channel blockers on the acetylcholine (ACh)-induced relaxation of vascular smooth muscle, intracellular free Ca2+ concentration ([Ca2+]i) elevation, and ACh-evoked outward K+ current of endothelial cells of rabbit aorta were studied using bioassay, spectrofluorimetry, and patch-clamp techniques, respectively. In bioassay experiments, ACh caused relaxation of endothelium-denuded aortic rings in a concentration-dependent manner when perfused through an endothelium-intact donor segment of aorta but not when perfused directly onto the recipient aortic ring. ACh-induced relaxation was inhibited by perfusion of tetraethylammonium ions (TEA; 5 mM) through the donor but not by perfusion directly onto the recipient segment. Glibenclamide had no effect on ACh-induced relaxation of the bioassay ring in either situation. ACh increased [Ca2+]i at the endothelial surface of aortic strips but not at the adventitial surface. TEA inhibited ACh-induced [Ca2+]i elevation, whereas glibenclamide had no effect. In patch-clamp experiments with freshly isolated endothelial cells, ACh evoked a biphasic outward current which was completely abolished by TEA (3 mM). It is concluded that Ca(2+)-dependent K+ channels are important for increasing [Ca2+]i during agonist stimulation and consequently for the synthesis/release of endothelium-derived relaxing factors (EDRFs). Furthermore, endothelial ATP-sensitive K+ channels do not contribute to ACh-induced relaxation or evoke an increase in endothelial [Ca2+]i of rabbit thoracic aorta.

scholarly journals Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4525
Author(s):  
Wei-Ting Chang ◽  
Ping-Yen Liu ◽  
Sheng-Nan Wu
Keyword(s):  
T Lymphocytes ◽  
Immune Cells ◽  
K Channel ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Dependent Manner ◽  
Inactivation Curve ◽  
K Channels ◽  
Sphingosine 1 Phosphate ◽  
K Current

FTY720 (fingolimod), a modulator of sphingosine-1-phosphate receptors, is known to produce the immunomodulatory actions and to be beneficial for treating the relapsing multiple sclerosis. However, whether it exerts any effects on membrane ion currents in immune cells remains largely unknown. Herein, the effects of FTY720 on ionic currents in Jurkat T-lymphocytes were investigated. Cell exposure to FTY720 suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 1.51 μM. Increasing the FTY720 concentration not only decreased the IK(DR) amplitude but also accelerated the inactivation time course of the current. By using the minimal reaction scheme, the effect of FTY720 on IK(DR) inactivation was estimated with a dissociation constant of 3.14 μM. FTY720 also shifted the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor, and recovery from IK(DR) became slow during the exposure to this compound. Cumulative inactivation for IK(DR) in response to repetitive depolarizations was enhanced in the presence of FTY720. In SEW2871-treated cells, FTY720-induced inhibition of IK(DR) was attenuated. This compound also exerted a stimulatory action on the activity of intermediate-conductance Ca2+-activated K+ channels in Jurkat T-lymphocytes. However, in NSC-34 neuronal cells, FTY720 did not modify the inactivation kinetics of KV3.1-encoded IK(DR), although it suppressed IK(DR) amplitude in these cells. Collectively, the perturbations by FTY720 on different types of K+ channels may contribute to the functional activities of immune cells, if similar findings appear in vivo.

scholarly journals The Distribution of Activation Markers and Selectins on Peripheral T Lymphocytes in Preeclampsia

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Anna Bajnok ◽  
Maria Ivanova ◽  
János Rigó ◽  
Gergely Toldi
Keyword(s):  
T Lymphocytes ◽  
Adhesion Molecules ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
Cellular Adhesion ◽  
Cell Surface Expression ◽  
Specific Cell ◽  
Neutrophil Granulocytes ◽  
Activation Markers ◽  
T Lymphocyte Activation

Introduction. Impaired maternal immune tolerance resulting in systemic inflammation plays a pivotal role in the pathogenesis of preeclampsia. Phenotypical changes of monocytes and neutrophil granulocytes have already been studied in preeclampsia, and some studies also included T lymphocyte activation markers; however, the results are controversial and a comprehensive analysis of activation markers is lacking. The characteristics of cellular adhesion molecules in preeclampsia are yet to be described.Material and Methods. Peripheral blood samples of 18 preeclamptic patients and 20 healthy pregnant women in the third trimester were evaluated using flow cytometry to characterize the cell surface expression of T lymphocyte activation markers and selectins.Results. We found an elevated ratio of HLA-DR and CD122-, CD62E-, and CD62L-expressing cells among the CD4+ T lymphocytes in PE in comparison to healthy pregnancy. No alterations were found in the prevalence of CD69-, CD25-, and CD62P-expressing lymphocytes and CD11c-expressing monocytes.Conclusions. Our findings support the role of activated T lymphocytes and specific cell adhesion molecules in the pathogenesis of preeclampsia.

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