scholarly journals Pentoxifylline Restores T Cell Viability in Hyper-inflammatory Conditions

2020 ◽  
Author(s):  
Sung-Jun Park ◽  
Sung-Hyuk Choi ◽  
Young-Duck Cho ◽  
Jung-Youn Kim ◽  
Han-Jin Cho ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Viability ◽  
Interleukin 2 ◽  
Cell Interaction ◽  
Jurkat Cells ◽  
Cell Mediated Immunity ◽  
Western Blots ◽  
Inflammatory Conditions ◽  
Tnf Α

Abstract Background: Immunity is the state of having sufficient biological defenses to avoid infection, trauma, or other unwanted biological invasions. T-cells and macrophages play important role in cell-mediated immunity. Pentoxifylline (PTX) is known to decrease pro-inflammatory cytokine and tumor necrosis factor (TNF-α). However, the effect on the immune system is not known well. This study aims to investigate the effect of PTX on inflammation. Methods: THP-1 derived macrophages were incubated with lipopolysaccharide (LPS) and/or indicated concentration of PTX for 8hr and wash with PBS to eliminate the effect of LPS. In this media, Jurkat cells were plated into trans-well plate and co-culture was done at 12hr. The T cell viability was measured by MTT. Also, the expression of Interleukin-2 (IL-2) was analyzed by RT-PCR and western blots. Results: PTX restored the increased concentration of MIF, TLR4 protein level and mRNA expression of TLR4 in LPS stimulated THP-1 derived macrophages. However, PTX did not restore the decreased T cell proliferation with PGE2 in Jurkat cells. In the co-culture study, The T cell viability was decreased in the THP-1 derived macrophage cells stimulated with LPS. The additional PTX restored the T cell's viability. Besides, PTX restored the decrease in the IL-2 expression of Jurkat cells in the LPS stimulated THP-1 derived macrophages. Conclusion: LPS stimulated THP-1 derived macrophages inhibited the T cell viability in hyper-inflammation conditions. However, PTX restored the T cells viability with increase IL-2. PTX influenced the cell-cell interaction, therefore, had its immunomodulatory effects.

scholarly journals Macrophage-T Cell Interaction Is Essential for the Induction of p75 Interleukin 2 (IL-2) Receptor and IL-2 Responsiveness in Human CD4+T Cells

1991 ◽  
Vol 82 (3) ◽  
pp. 257-261 ◽  
Author(s):  
Yoshihiko Nakamura ◽  
Takashi Nishimura ◽  
Yutaka Tokuda ◽  
Nobumasa Kobayashi ◽  
Katsuto Watanabe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Cell Interaction

scholarly journals SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell–mediated immunity

Science ◽  
2021 ◽  
Vol 372 (6543) ◽  
pp. eaba4220 ◽  
Author(s):  
Tao Yue ◽  
Xiaoming Zhan ◽  
Duanwu Zhang ◽  
Ruchi Jain ◽  
Kuan-wen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Cell Mediated Immunity ◽  
Activated T Cells ◽  
Granule Formation

Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell–specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2’s mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

The effects of oxygen and medicines on T cells in hypoxic co-culture

2021 ◽  
Keyword(s):  
T Cells ◽  
Cell Viability ◽  
Oxygen Supply ◽  
Interleukin 2 ◽  
Hypoxic Condition ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Trauma Patients ◽  
Low Oxygen ◽  
Western Blots

Objectives: Many patients with massive hemorrhage, respiratory failure due to trauma admit the emergency department, and further that the experience can fall into shock, inducing to sepsis, multiple organ failure due to hyperinflammation or immunosuppression. In the these patients, the low oxygen flow with immunosuppression is believed to play a significant role. Hence, oxygen supply and medicines is essential in severe trauma patients. Therefore, this study aims to investigate the effects of oxygen and variable medicines in hypoxic condition. Methods: T cells and macrophages were plated into trans-well plate for co-culture for 30 minutes in hypoxia. After that, the cells were stimulated with lipopolysaccharide (LPS) followed by variable medicines by normoxia or oxygen supply for 2 hrs and cells were inculated overnight under normoxic conditions. The T cell viability was measured by MTT, and the expression of interleukin-2 (IL-2), interleukin-8 (IL-8) and macrophage migration inhibitory factor (MIF) were measured by western blots using the T cells with co-culture with inflammatory maccrophages. Also, the concentration of MIF was analyzed by ELISA. Results: The T cells viability was decreased in hypoxia with LPS stimulation, however, pentoxifylline (PTX) effectively restored cell viability regardless of oxygen state (p < 0.05). Besides, PTX in oxygen supply status restored the decreases in IL-2 expression of T cells and the increases MIF in the LPS stimulation with hypoxia (p < 0.05). Conclusions: PTX has more effectively restored the T cells immunosuppression in hypoxia during oxygen supply, and has an immunomodulation effect by controlling hyperinflammation.

scholarly journals Stimulation of T cells through the CD3/T-cell receptor complex: role of cytoplasmic calcium, protein kinase C translocation, and phosphorylation of pp60c-src in the activation pathway.

1987 ◽  
Vol 7 (2) ◽  
pp. 650-656 ◽  
Author(s):  
J A Ledbetter ◽  
L E Gentry ◽  
C H June ◽  
P S Rabinovitch ◽  
A F Purchio
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Solid Phase ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Receptor Complex ◽  
Kinase C ◽  
Stimulation Of

Stimulation of T cells or the Jurkat T-cell line with soluble antibodies to the CD3/T-cell receptor complex causes mobilization of cytoplasmic Ca2+, which is blocked by pertussis toxin but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and translocation of protein kinase C activity from the cytoplasm to the membrane. Such stimulation also causes phosphorylation of pp60c-src at an amino-terminal serine residue. These activities are consistent with induction of phosphatidylinositol metabolism after antibody binding. Anti-CD3 stimulation with antibody in solution, however, does not cause Jurkat cells to release interleukin 2 and blocks rather than induces proliferation of T cells. Induction of interleukin 2 production by Jurkat cells and proliferation by normal T cells requires anti-CD3 stimulation with antibody on a solid support, such as Sepharose beads or a plastic dish. Thus, we examined phosphorylation of pp60c-src after stimulation of Jurkat cells with anti-CD3 in solution or on solid phase. Both of these caused serine phosphorylation of pp60c-src that was indistinguishable even after 4 h of stimulation. These results indicate that the mode of anti-CD3 stimulation (in solution or on solid phase) controls a cellular function that modifies the consequences of signal transduction through phosphatidylinositol turnover.

scholarly journals Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluble antigen arrays.

1992 ◽  
Vol 176 (5) ◽  
pp. 1421-1430 ◽  
Author(s):  
D E Symer ◽  
R Z Dintzis ◽  
D J Diamond ◽  
H M Dintzis
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Jurkat Cells ◽  
Soluble Antigen ◽  
Human T Cell ◽  
Human T Cells ◽  
Binding Avidity

We present evidence that direct T cell receptor (TCR) occupancy by antigen can either activate or inhibit T cells, depending upon whether or not a threshold number of local TCRs are crosslinked by multivalent arrays of the antigen. Variants of Jurkat cells were previously transfected with TCR alpha and beta chains that bind fluorescein, yielding FL-TCR+ human T cells. The transfectants are activated upon binding soluble multivalent antigen arrays at concentrations well below those required for monovalent interactions. This activation, measured by calcium fluxes and interleukin 2 (IL-2) production, indicates the superior binding avidity of multivalent ligands. Smaller, less multivalent arrays do not activate the cells, but antagonize larger arrays, demonstrating that antigen can bind TCR as either agonist or antagonist. The balance between activation and inhibition depends upon antigen array size, ligand valence, and concentration, indicating that a threshold extent of receptor crosslinking, and not individual perturbations of single TCR, is required for activation by antigen. Approximately 100 stimulatory arrays specifically bind per FL-TCR+ cell at concentrations where IL-2 production is half-maximal.

scholarly journals Differential Regulation of Cytokine Production by CD1d-Restricted NKT Cells in Response to Superantigen Staphylococcal Enterotoxin B Exposure

2006 ◽  
Vol 74 (1) ◽  
pp. 282-288 ◽  
Author(s):  
Melanie J. Ragin ◽  
Nisebita Sahu ◽  
Avery August
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Nkt Cells ◽  
Staphylococcal Enterotoxin ◽  
Cytokine Secretion ◽  
Staphylococcal Enterotoxin B ◽  
Tnf Α ◽  
Ifn Γ ◽  
Enterotoxin B

ABSTRACT NKT cells are a heterogeneous population characterized by the ability to rapidly produce cytokines, such as interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-γ) in response to infections by viruses, bacteria, and parasites. The bacterial superantigen staphylococcal enterotoxin B (SEB) interacts with T cells bearing the Vβ3, -7, or -8 T-cell receptors, inducing their expansion and cytokine secretion, leading to death in some cases due to cytokine poisoning. The majority of NKT cells bear the Vβ7 or -8 T-cell receptor, suggesting that they may play a role in regulating this response. Using mice lacking NKT cells (CD1d−/− and Jα18−/− mice), we set out to identify the role of these cells in T-cell expansion, cytokine secretion, and toxicity induced by exposure to SEB. We find that Vβ8+ CD4+ T-cell populations similarly expand in wild-type (WT) and NKT cell-null mice and that NKT cells did not regulate the secretion of IL-2. By contrast, these cells positively regulated the secretion of IL-4 and IFN-γ production and negatively regulated the secretion of tumor necrosis factor alpha (TNF-α). However, this negative regulation of TNF-α secretion by NKT cells provides only a minor protective effect on SEB-mediated shock in WT mice compared to mice lacking NKT cells. These data suggest that NKT cells may regulate the nature of the cytokine response to exposure to the superantigen SEB and may act as regulatory T cells during exposure to this superantigen.

scholarly journals Transfer of Mycoplasma hyopneumoniae-specific cell mediated immunity to neonatal piglets

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Evelien Biebaut ◽  
Lisa Beuckelaere ◽  
Filip Boyen ◽  
Freddy Haesebrouck ◽  
Charles-Oliver Gomez-Duran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mycoplasma Hyopneumoniae ◽  
T Cell Subsets ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Neonatal Piglets ◽  
Tnf Α ◽  
Primary Agent

AbstractMycoplasma hyopneumoniae is the primary agent of enzootic pneumonia in pigs. Although cell mediated immunity (CMI) may play a role in protection against M. hyopneumoniae, its transfer from sows to their offspring is poorly characterized. Therefore, maternally-derived CMI was studied in piglets from vaccinated and non-vaccinated sows. The potential influence of cross-fostering before colostrum ingestion on the transfer of CMI from dam to piglets was also investigated. Six M. hyopneumoniae vaccinated sows from an endemically infected herd and 47 of their piglets, of which 24 piglets were cross-fostered, were included, as well as three non-vaccinated control sows from an M. hyopneumoniae-free herd and 24 of their piglets. Vaccinated sows received a commercial bacterin intramuscularly at 6 and 3 weeks prior to farrowing. The TNF-α, IFN-γ and IL-17A production by different T-cell subsets in blood of sows, colostrum and blood of piglets was assessed using a recall assay. In blood of sows cytokine producing T-cells were increased upon M. hyopneumoniae vaccination. Similarly, M. hyopneumoniae-specific T-cells were detected in blood of 2-day-old piglets born from these vaccinated sows. In contrast, no M. hyopneumoniae-specific cytokine producing T-cells were found in blood of piglets from control sows. No difference was found in M. hyopneumoniae-specific CMI between cross-fostered and non-cross-fostered piglets. In conclusion, different M. hyopneumoniae-specific T-cell subsets are transferred from the sow to the offspring. Further studies are required to investigate the role of these transferred cells on immune responses in piglets and their potential protective effect against M. hyopneumoniae infections.

scholarly journals The Trend of TIM3 Expression on T Cells in Patients With Nontuberculous Mycobacterial Lung Disease: From Immune Cell Dysfunction to Clinical Severity

2021 ◽  
Vol 12 ◽  
Author(s):  
Ping-Huai Wang ◽  
Ming-Fang Wu ◽  
Chi-Yu Hsu ◽  
Sheng-Wei Pan ◽  
Chin-Chung Shu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Disease ◽  
Cd8 T Cells ◽  
Cell Apoptosis ◽  
Interleukin 2 ◽  
Clinical Severity ◽  
Cd4 Cells ◽  
Nontuberculous Mycobacterial Lung Disease ◽  
Tnf Α

BackgroundThe incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide. Immune exhaustion has been reported in NTM-LD, but T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a co-inhibitory receptor on T cells, has been scarcely studied.MethodsPatients with NTM-LD and healthy controls were prospectively recruited from July 2014 to August 2019 at three tertiary referral centers in Taiwan. We examined TIM3 expression on the T cells from the participants using flow cytometry. TIM3 expression was analyzed for different disease statuses and after treatment. The apoptosis and cytokine profiles were analyzed according to the TIM3 expression.ResultsAmong enrolled subjects (47 patients and 46 controls), TIM3 on CD4+ cells (6.44% vs. 4.12%, p = 0.028) and CD8+ cells (18.47% vs. 9.13%, p = 0.003) were higher in NTM-LD patients than in the controls. The TIM3 level on CD4+ and CD8+ T cells was positively associated with T-cell apoptosis in the NTM-LD patients. In stimulating peripheral blood mononuclear cells using PMA plus ionomycin, a high TIM3 level on T cells correlated with low interleukin-2 and tumor necrosis factor-alpha (TNF-α) on CD4+ cells and interferon-gamma and TNF-α on CD8+ T cells. For clinical manifestation, low body mass index (BMI), positive sputum acid-fast smear, and high radiographic score correlated with high TIM3 expression on T cells. After NTM treatment, TIM3+ decreased significantly on CD4+ and CD8+ T cells.ConclusionsIn patients with NTM-LD, TIM3+ expression increased over CD4+ and CD8+ T cells and correlated with cell apoptosis and specific cytokine attenuation. Clinically, TIM3+ T cells increased in patients with low BMI, high disease extent, and high bacilli burden but decreased after treatment.

scholarly journals Measles Virus Suppresses Cell-mediated Immunity by Interfering with the Survival and Functions of Dendritic and T Cells

1997 ◽  
Vol 186 (6) ◽  
pp. 813-823 ◽  
Author(s):  
Isabelle Fugier-Vivier ◽  
Christine Servet-Delprat ◽  
Pierre Rivailler ◽  
Marie-Clotilde Rissoan ◽  
Yong-Jun Liu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Measles Virus ◽  
Cell Function ◽  
Cell Interaction ◽  
Cell Mediated Immunity ◽  
High Morbidity ◽  
Pulsed Dc ◽  
Activated Monocytes ◽  
Syncytia Formation

Secondary infections due to a marked immunosuppression have long been recognized as a major cause of the high morbidity and mortality rate associated with acute measles. The mechanisms underlying the inhibition of cell-mediated immunity are not clearly understood but dysfunctions of monocytes as antigen-presenting cells (APC) are implicated. In this report, we demonstrate that measles virus (MV) replicates weakly in the resting dendritic cells (DC) as in lipopolysaccharide-activated monocytes, but intensively in CD40-activated DC. The interaction of MV-infected DC with T cells not only induces syncytia formation where MV undergoes massive replication, but also leads to an impairment of DC and T cell function and cell death. CD40-activated DC decrease their capacity to produce interleukin (IL) 12, and T cells are unable to proliferate in response to MV-infected DC stimulation. A massive apoptosis of both DC and T cells is observed in the MV pulsed DC–T cell cocultures. This study suggests that DC represent a major target of MV. The enhanced MV replication during DC–T cell interaction, leading to an IL-12 production decrease and the deletion of DC and T cells, may be the essential mechanism of immunosuppression induced by MV.

scholarly journals Differentiation of Antigen-Specific T Cells with Limited Functional Capacity during Mycobacterium tuberculosis Infection

2013 ◽  
Vol 82 (1) ◽  
pp. 132-139 ◽  
Author(s):  
Yun Hee Jeong ◽  
Bo-Young Jeon ◽  
Sun-Hwa Gu ◽  
Sang-Nae Cho ◽  
Sung Jae Shin ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Memory T Cells ◽  
Interleukin 2 ◽  
Effector Memory ◽  
Memory Cells ◽  
Content Type ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTDespite the generation ofMycobacterium tuberculosis-specific T cell immune responses during the course of infection, only 5 to 10% of exposed individuals develop active disease, while others develop a latent infection. This phenomenon suggests defectiveM. tuberculosis-specific immunity, which necessitates more careful characterization ofM. tuberculosis-specific T cell responses. Here, we longitudinally analyzed the phenotypes and functions ofM. tuberculosis-specific T cells. In contrast to the functional exhaustion of T cells observed after chronic infection,M. tuberculosis-specific CD8+T cells differentiated into either effector (CD127loCD62Llo) or effector memory (CD127hiCD62Llo) cells, but not central memory cells (CD127hiCD62Lhi), with low programmed death 1 (PD-1) expression, even in the presence of high levels of bacteria. Additionally,M. tuberculosis-specific CD8+and CD4+T cells produced substantial levels of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), but not interleukin 2 (IL-2), uponin vitrorestimulation. AmongM. tuberculosis-specific CD8+T cells, CD127hieffector memory cells displayed slower ongoing turnover but greater survival potential. In addition, these cells produced more IFN-γ and TNF-α and displayed lytic activity upon antigen stimulation. However, the effector function ofM. tuberculosis-specific CD8+CD127hieffector memory T cells was inferior to that of canonical CD8+CD127himemory T cells generated after acute lymphocytic choriomeningitis virus infection. Collectively, our data demonstrate thatM. tuberculosis-specific T cells can differentiate into memory T cells during the course ofM. tuberculosisinfection independent of the bacterial burden but with limited functionality. These results provide a framework for further understanding the mechanisms ofM. tuberculosisinfection that can be used to develop more effective vaccines.

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