scholarly journals The Dual Role of the β2-Adrenoreceptor in the Modulation of IL-17 and IFN-γ Production by T Cells in Multiple Sclerosis

2022 ◽  
Vol 23 (2) ◽  
pp. 668
Author(s):  
Mikhail Melnikov ◽  
Vladimir Rogovskii ◽  
Anastasiya Sviridova ◽  
Anna Lopatina ◽  
Mikhail Pashenkov ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Ifn Γ

Norepinephrine is a neurotransmitter that also has an immunomodulatory effect and is involved in multiple sclerosis (MS) pathogenesis. This study aimed to clarify the role of the β2-adrenoreceptor in the norepinephrine-mediated modulation of interleukin-17 (IL-17) and interferon-γ (IFN-γ) production, which play a critical pathogenetic role in MS. CD4+ T cells obtained from twenty-five relapsing-remitting MS patients and sixteen healthy subjects were cultured ex vivo with norepinephrine and/or β2-adrenoreceptor antagonist or agonist, followed by a cytokine production analysis using ELISA. Norepinephrine suppressed IL-17 and IFN-γ production by the anti-CD3/anti-CD28-microbead-stimulated CD4+ T cells in both groups. Blockade of the β2-adrenoreceptor with the specific antagonist ICI 118.551 enhanced norepinephrine-mediated IL-17 suppression but decreased its inhibitory effect on IFN-γ production in MS patients. In contrast, the β2-adrenoreceptor agonist formoterol did not influence norepinephrine’s inhibitory effect on cytokine production in both groups. The blockade of the β2-adrenoreceptor, even in the absence of exogenous norepinephrine, suppressed IL-17 production but did not influence IFN-γ production in both groups. Conversely, β2-adrenoreceptor activation by formoterol decreased IFN-γ production and did not affect IL-17 production in both groups. These data illustrate the inhibitory effect of norepinephrine on IL-17 and IFN-γ production by CD4+ T cells in MS. The inhibitory effect of norepinephrine on IFN-γ production by CD4+ T cells in MS could be mediated via β2-adrenoreceptor activation.

The role of D2-like dopaminergic receptor in dopamine-mediated modulation of Th17-cells in multiple sclerosis

2021 ◽  
Vol 19 ◽  
Author(s):  
Mikhail Melnikov ◽  
Anastasiya Sviridova ◽  
Vladimir Rogovskii ◽  
Vladimir Kudrin ◽  
Vladimir Murugin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Healthy Subjects ◽  
Th17 Cells ◽  
Cell Activity ◽  
Interleukin 17 ◽  
Dopaminergic Receptor ◽  
Gm Csf ◽  
Ifn Γ

: Dopamine is a direct mediator of neuroimmune interaction and may play a significant role in multiple sclerosis (MS) pathogenesis by modulating immune cell activity and cytokine production. We studied the effects of dopamine on Th17-cells function in 34 patients with relapsing-remitting MS and 23 healthy subjects. Production of interleukin-17 (IL-17), interferon-γ (IFN-γ), granulocyte-colony stimulating factor (GM-CSF), and IL-21 by CD4+ T-cells as well as dopamine were comparable between the groups. Dopamine suppressed IL-17, IFN-γ, GM-CSF, and IL-21 production by stimulated СD4+ T-cells in both groups. Blockade of D1-like dopaminergic receptor with a specific antagonist SCH23390 did not affect dopamine-mediated cytokine suppression. In contrast, blockade of D2-like dopaminergic receptor by sulpiride decreased dopamine's inhibitory effect on IL-17 secretion in both groups and GM-CSF and IL-21 production in MS patients. Blockade of D1-like dopaminergic receptor directly inhibited IL-17, IFN-γ, GM-CSF in both groups and IL-21 production in healthy subjects, while blockade of D2-like dopaminergic receptor had no effect on cytokine secretion. Finally, activation of D2-like dopaminergic receptor with a specific agonist quinpirole decreased IL-17, IFN-γ, and GM-CSF production in both groups. These data suggest an inhibitory role of dopamine on Th17-cells in MS, which could be mediated by the activation of D2-like dopaminergic receptor.

scholarly journals The JAK inhibitor tofacitinib regulates synovitis through inhibition of interferon-γ and interleukin-17 production by human CD4+ T cells

2012 ◽  
Vol 64 (6) ◽  
pp. 1790-1798 ◽  
Author(s):  
Keisuke Maeshima ◽  
Kunihiro Yamaoka ◽  
Satoshi Kubo ◽  
Kazuhisa Nakano ◽  
Shigeru Iwata ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Jak Inhibitor

scholarly journals Cytokine production in ex-vivo stimulated fresh and cryopreserved T-cells

2021 ◽  
Vol 67 (2) ◽  
pp. 95-101
Author(s):  
Monica Vuță ◽  
Ionela-Maria Cotoi ◽  
Ion Bogdan Mănescu ◽  
Doina Ramona Manu ◽  
Minodora Dobreanu
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Gradient Centrifugation ◽  
Intracellular Cytokine Staining ◽  
Interleukin 2 ◽  
Middle Aged

Abstract Objective: In vitro cytokine production by peripheral blood mononuclear cells (PBMCs) is an important and reliable measure of immunocompetence. PBMC can be stimulated directly after isolation or frozen for later use. However, cryopreservation may affect cell recovery, viability and functionality. This study aims to investigate cytokine synthesis in ex-vivo stimulated fresh and cryopreserved CD4+ and CD4- T cells. Methods: PBMCs were obtained by Ficoll gradient centrifugation from heparinized peripheral blood of 6 middle-aged clinically healthy subjects. Half of these cells (labeled “Fresh”) was further processed and the other half (labeled “Cryo”) was cryopreserved at -140°C for up to 3 months. Fresh-PBMCs were activated with Phorbol-Myristate-Acetate/Ionomycin/Monensin for 5 hours immediately after isolation while Cryo-PBMCs were identically activated after thawing and cell resting. Activated cells were fixed, permeabilized and intracellular cytokine staining was performed using Phycoerythrin (PE)-conjugated antibodies for Interleukin-2 (IL-2), Tumor Necrosis Factor-alpha (TNF-a), and Interferon-gamma (IFN-g). All samples were analyzed within 24 hours by flow cytometry. Results: Both Fresh and Cryo CD3+CD4+/CD3+CD4- sub-populations partially produced each of the three cytokines. A higher percentage of CD4+ T cells produced IL-2 and TNF-a and a greater percentage of CD4- T cells were found to produce IFN-g. A significantly higher percentage of Cryo-lymphocytes was shown to produce TNF-a in both CD3+CD4+ (31.4% vs 24.9%, p=0.031) and CD3+CD4- (22.7% vs 17.9%, p=0.031) subpopulations. No notable difference was found for IL-2 and IFN-g production between Fresh and Cryo T cells. Conclusion: Cryopreservation for up to 3 months significantly increases TNF-a production of T-cells in clinically healthy middle-aged subjects.

scholarly journals The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Yong Tang ◽  
Marie J. Desierto ◽  
Jichun Chen ◽  
Neal S. Young
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Transcription Factor ◽  
Transforming Growth Factor ◽  
Bone Marrow Failure ◽  
Critical Role ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Immune Mediated

Abstract The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet−/−). In comparison with normal C57BL6 (B6) control mice, T-bet−/− mice had normal cellular composition in lymphohematopoietic tissues, but T-bet−/− lymphocytes were functionally defective. Infusion of 5 × 106 T-bet−/− lymph node (LN) cells into sublethally irradiated, major histocompatibility complex–mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet−/− LN-cell dose to 10 to 23 × 106 per recipient led to only mild hematopoietic deficiency. Recipients of T-bet−/− LN cells had no expansion in T cells or interferon-γ–producing T cells but showed a significant increase in Lin−Sca1+CD117+CD34− BM cells. Plasma transforming growth factor-β and interleukin-17 concentrations were increased in T-bet−/− LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-γ resulted in hematopoietic suppression but did not cause T-bet−/− LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope

2021 ◽  
Vol 218 (10) ◽  
Author(s):  
Sarah A. Greaves ◽  
Avinash Ravindran ◽  
Radleigh G. Santos ◽  
Lan Chen ◽  
Michael T. Falta ◽  
...  
Keyword(s):  
T Cells ◽  
Aspergillus Nidulans ◽  
Cd4 T Cells ◽  
Antigen Specificity ◽  
Igg Antibody ◽  
Löfgren’S Syndrome ◽  
Acute Form ◽  
Ifn Γ ◽  
Hla Dr3

Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.

Clinical significance of cytokine markers in children with different courses of community-acquired pneumonia

2020 ◽  
Vol 15 (5) ◽  
pp. 18-23
Author(s):  
G.P. Evseeva ◽  
◽  
G.N. Kholodok ◽  
S.V. Pichugina ◽  
S.V. Suprun ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Interleukin 1 ◽  
Interferon Γ ◽  
Peripheral Blood Lymphocytes ◽  
Community Acquired Pneumonia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Ifn Γ

Principles of the diagnosis and treatment of community-acquired pneumonia (CAP) in children were developed and clearly formulated long ago. Nevertheless, clinicians often encounter the problem of pulmonary and pleural complications of CAP, which is challenging in terms of the choice of initial therapy, since the first symptoms of uncomplicated and complicated pneumonia are often similar. Therefore, the search for early markers of complicated CAP in children is highly important. Objective. To assess prognostic values of spontaneous and mitogen-induced cytokine production in children with CAP. Patients and methods. We have performed comprehensive examination of 108 children with CAP. Eighty-four of them had uncomplicated CAP, whereas 24 children had CAP complicated by pleurisy. We measured spontaneous and induced production of the following cytokines upon patient admission to hospital: interleukin-1 (IL-1), interleukin-17 (IL-17), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). To measure induced cytokine production, we stimulated peripheral blood lymphocytes by S. рneumonае (serotype 7, 11; strains 7C and 11AD). The level of cytokines was evaluated using the enzyme-linked immunosorbent assay (Vektor-BEST, Novosibirsk, Russia). Results. We found that in children with uncomplicated CAP, induction of immunocompetent blood cells (IBCs) led to increased secretion of first-generation cytokines, including IL-1, TNF-α, and IFN-γ, whereas IBCs of patients with complicated CAP primarily produced second-generation cytokines, including VEGF, МРС-1, and IL-17. Conclusion. The observed differences in spontaneous and mitogen-induced cytokine production between children with and without CAP complications suggest that these parameters can be considered as promising prognostic markers for complicated CAP in children. The proposed method can be used in pediatric practice to predict the development of complications in children with CAP. Key words: children, community-acquired pneumonia, cytokines

scholarly journals Beneficial effect of co-polymer 1 on cytokine production by CD4 T cells in multiple sclerosis

Immunology ◽  
2001 ◽  
Vol 104 (4) ◽  
pp. 383-391 ◽  
Author(s):  
BenoiT Fellay ◽  
Michel Chofflon ◽  
Catherine Juillard ◽  
Anne-Marie Paunier ◽  
Theodor Landis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Beneficial Effect ◽  
Cd4 T Cells ◽  
Cytokine Production

scholarly journals Aberrant Contraction of Antigen-Specific CD4 T Cells after Infection in the Absence of Gamma Interferon or Its Receptor

2006 ◽  
Vol 74 (11) ◽  
pp. 6252-6263 ◽  
Author(s):  
Jodie S. Haring ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Gamma Interferon ◽  
Model Systems ◽  
Important Regulator ◽  
Ifn Γ ◽  
And Function ◽  
Deficient Mice

ABSTRACT Several lines of evidence from different model systems suggest that gamma interferon (IFN-γ) is an important regulator of T-cell contraction after antigen (Ag)-driven expansion. To specifically investigate the role of IFN-γ in regulating the contraction of Ag-specific CD4 T cells, we infected IFN-γ−/− and IFN-γR1−/− mice with attenuated Listeria monocytogenes and monitored the numbers of Ag-specific CD4 T cells during the expansion, contraction, and memory phases of the immune response to infection. In the absence of IFN-γ or the ligand-binding portion of its receptor, Ag-specific CD4 T cells exhibited normal expansion in numbers, but in both strains of deficient mice there was very little decrease in the number of Ag-specific CD4 T cells even at time points later than day 90 after infection. This significant delay in contraction was not due to prolonged infection, since mice treated with antibiotics to conclusively eliminate infection exhibited the same defect in contraction. In addition to altering the number of Ag-specific CD4 T cells, the absence of IFN-γ signaling also changed the phenotype of cells generated after infection. IFN-γR1−/− Ag-specific CD4 T cells reacquired expression of CD127 more quickly than wild-type cells, and more IFN-γR1−/− CD4 T cells were capable of producing both IFN-γ and interleukin 2 following Ag stimulation. From these data we conclude that IFN-γ regulates the contraction, phenotype, and function of Ag-specific CD4 T cells generated after infection.

scholarly journals Disruption of Interleukin-27 Signaling Results in Impaired Gamma Interferon Production but Does Not Significantly Affect Immunopathology in Murine Schistosome Infection

2007 ◽  
Vol 75 (6) ◽  
pp. 3169-3177 ◽  
Author(s):  
Mara G. Shainheit ◽  
Rosita Saraceno ◽  
Lindsey E. Bazzone ◽  
Laura I. Rutitzky ◽  
Miguel J. Stadecker
Keyword(s):  
T Cells ◽  
Proinflammatory Cytokines ◽  
Cd4 T Cells ◽  
Granulomatous Inflammation ◽  
Gamma Interferon ◽  
Mouse Strains ◽  
Interleukin 17 ◽  
Schistosome Infection ◽  
Ifn Γ

ABSTRACT In schistosomiasis mansoni, parasite eggs cause hepatointestinal granulomatous inflammation and fibrosis mediated by CD4 T cells specific for egg antigens. The severity of disease varies extensively in humans and among mouse strains. Marked disease exacerbation induced in typically low-pathology C57BL/6 mice by immunization with schistosome egg antigens (SEA) in complete Freund's adjuvant (SEA/CFA) correlates with elevated production of the proinflammatory cytokines gamma interferon (IFN-γ) and interleukin-17 (IL-17), which are regulated by IL-12 and IL-23, respectively. Here we examined the effect on the schistosome infection of a third member of the IL-12 family of heterodimeric cytokines, IL-27, using SEA/CFA-immunized and unimmunized mice deficient in the IL-27 receptor chain WSX-1 (WSX-1−/−). SEA-stimulated bulk mesenteric lymph node cells or CD4 T cells from 7-week-infected WSX-1−/− mice produced significantly less IFN-γ than did those from C57BL/6 mice, even though there was no difference between these mice in exacerbated hepatic egg-induced granulomatous inflammation or in the levels of IL-17 induced by immunization with SEA/CFA. A fraction of the cells in the granulomas stained positive for IL-27, but there were no significant differences between WSX-1−/− and BL/6 mice, nor were there differences in the number of CD4 T cells and eosinophils. A 24-week chronic infection resulted in markedly reduced levels of proinflammatory cytokines, including IFN-γ, in WSX-1−/− mice, but again the magnitude of immunopathology was not significantly different between the two groups. These findings indicate that despite the impaired IFN-γ production, IL-27 signaling has no significant effect on either the magnitude of egg-induced immunopathology or on its closest in vitro correlate, IL-17.

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