Cytokine Production by Peripheral Blood CD4+and CD8+T Cells in Atopic Childhood Asthma

There are conflicting studies on T cell cytokine production in childhood asthma. In this study intracellular cytokine expression of IL-2, IL-4, IL-10, IL-13, IFN-γ, and TNF-α in CD4+and CD8+T cells in children with atopic asthma were measured by flow cytometry.Results. A significant increase in the percentage of CD4+and CD8+T cells producing IL-4 and IL-13 and decrease in the percentage of CD4+producing IFN-γ in asthmatic children was found. The percentage of CD4+/IL-13+was significantly higher in severe asthma than in children with intermittent disease symptoms. Severity of asthma was associated with increased both serum IgE and frequencies of CD4+/IL-13+T cells, as well as duration of disease. Moreover, a decrease in FEV1, FEV1/FVC was observed in relation to the severity of asthma. Changes in cytokine profile in CD8+subpopulation didn't depend on the severity of the disease.Conclusions. Increased production of IL-4 and IL-13 in both CD4+and CD8+T cells accompanied by decreased IFN-γ expression in CD4+T cells may be evidence that both lymphocyte subpopulations are implicated in the pathogenesis of asthma. Relationship of CD4+/IL-13+T cells with disease activity suggests that this lymphocyte subset may have a prominent role in childhood asthma.

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Distinct PKC-mediated posttranscriptional events set cytokine production kinetics in CD8+ T cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1704227114 ◽

2017 ◽

Vol 114 (36) ◽

pp. 9677-9682 ◽

Cited By ~ 19

Author(s):

Fiamma Salerno ◽

Nahuel A. Paolini ◽

Regina Stark ◽

Marieke von Lindern ◽

Monika C. Wolkers

Keyword(s):

T Cells ◽

Mrna Stability ◽

Cytokine Production ◽

De Novo ◽

Translation Efficiency ◽

Mrna Stabilization ◽

Relative Contribution ◽

Production Kinetics ◽

Tnf Α ◽

Ifn Γ

Effective T cell responses against invading pathogens require the concerted production of three key cytokines: TNF-α, IFN-γ, and IL-2. The cytokines functionally synergize, but their production kinetics widely differ. How the differential timing of expression is regulated remains, however, poorly understood. We compared the relative contribution of transcription, mRNA stability, and translation efficiency on cytokine production in murine effector and memory CD8+ T cells. We show that the immediate and ample production of TNF-α is primarily mediated by translation of preformed mRNA through protein kinase C (PKC)-induced recruitment of mRNA to polyribosomes. Also, the initial production of IFN-γ uses translation of preformed mRNA. However, the magnitude and subsequent expression of IFN-γ, and of IL-2, depends on calcium-induced de novo transcription and PKC-dependent mRNA stabilization. In conclusion, PKC signaling modulates translation efficiency and mRNA stability in a transcript-specific manner. These cytokine-specific regulatory mechanisms guarantee that T cells produce ample amounts of cytokines shortly upon activation and for a limited time.

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"Tien-Hsien Liquid" Can Modulate Antigen-Stimulated Cytokine Production by T-Cells Isolated from Patients with Recurrent Aphthous Ulcerations

The American Journal of Chinese Medicine ◽

10.1142/s0192415x05003168 ◽

2005 ◽

Vol 33 (04) ◽

pp. 559-571 ◽

Cited By ~ 6

Author(s):

Andy Sun ◽

Jean-San Chia ◽

Won-Bo Wang ◽

Chun-Pin Chiang

Keyword(s):

T Cells ◽

Mononuclear Cells ◽

Cytokine Production ◽

Interferon Γ ◽

Enzyme Linked Immunosorbent Assay ◽

Peripheral Blood Mononuclear ◽

Tnf Α ◽

Ifn Γ ◽

Factor Α ◽

Necrosis Factor

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. Our previous study found that THL can modulate the antigen-stimulated proliferative response of peripheral blood mononuclear cells and T-cells isolated from RAU patients. In this study, we further tested whether THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. To achieve this goal, T-cells isolated from 19 RAU patients were incubated with phytohemagglutinin (PHA), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. The levels of interleukin (IL)-2, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, or IL-10 in the supernatants of T-cell cultures were measured by cytokine enzyme-linked immunosorbent assay (ELISA) kits. We found that THL significantly increased the PHA- or TT-stimulated TNF-α, IL-6, and IL-10 production by T-cells isolated from RAU patients. However, THL could also significantly decrease the TT-stimulated IL-2 production, the GtfD-stimulated IL-2, TNF-α, IL-6 and IL-10 production, and the S. mutans-stimulated IFN-γ, TNF-α, and IL-10 production by T-cells isolated from RAU patients. These results indicate that THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. Because RAU is probably a Thl-mediated disease with elevated levels of IL-2, IFN-γ, TNF-α and IL-6 in either the patient's sera or oral lesions and these increased levels of cytokines can be reduced by THL, we suggest that THL may be a potential immunoceutical agent for treatment of RAU.

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Spontaneous Cytokine Production and Its Effect on Induced Production

Clinical and Vaccine Immunology ◽

10.1128/cdli.9.5.1049-1056.2002 ◽

2002 ◽

Vol 9 (5) ◽

pp. 1049-1056 ◽

Cited By ~ 4

Author(s):

Derrick Walker ◽

Janine Jason ◽

Kelly Wallace ◽

Justin Slaughter ◽

Virginia Whatley ◽

...

Keyword(s):

T Cells ◽

Cytokine Production ◽

Ex Vivo ◽

Interleukin 2 ◽

Healthy Adults ◽

Multiparameter Flow Cytometry ◽

Parasitic Infections ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ifn Γ

ABSTRACT Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) by peripheral-blood B lymphocytes, T cells, CD8− T cells, CD8+ T cells, CD3− CD16/56+ lymphocytes (natural killer [NK] cells), CD3+ CD16/56+ lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-α production occurred most frequently, followed in descending order by IFN-γ, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-α; for 12 of these patients, TNF-α was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-α and IFN-γ, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.

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Dual Anti-Malarial and GSK3β-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria

Pharmaceuticals ◽

10.3390/ph14030248 ◽

2021 ◽

Vol 14 (3) ◽

pp. 248

Author(s):

Amatul Hamizah Ali ◽

Suhaini Sudi ◽

Ng Shi-Jing ◽

Wan Rozianoor Mohd Hassan ◽

Rusliza Basir ◽

...

Keyword(s):

Plasmodium Berghei ◽

Cytokine Production ◽

Glycogen Synthase ◽

Serum Levels ◽

Murine Models ◽

Malarial Infection ◽

Tnf Α ◽

Ifn Γ ◽

Severity Of The Disease ◽

Inflammatory Signalling

Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3β (GSK3β), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3β-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3β (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3β (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3β-mediated cytokine-modulating effects.

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B Cells Suppress IL-2, IFN-γ and TNF-α Production from Alloaggressive CD8+ T Cells in a Mismatched Murine Model of Bone Marrow Transplant.

Blood ◽

10.1182/blood.v108.11.5173.5173 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5173-5173

Author(s):

David S. Ritchie ◽

Victoria Watt

Keyword(s):

Bone Marrow ◽

T Cells ◽

T Cell ◽

B Cells ◽

Cd8 T Cells ◽

Cytokine Production ◽

Marrow Transplant ◽

Cell Engraftment ◽

Tnf Α ◽

Ifn Γ

Abstract B cells have been variously shown to induce direct tolerance of antigen specific CD8+ T cells in models of autoimmunity and tumor immunology. We have previously shown that resting B cells also inhibit anti-tumor T cell function and suppress graft versus host disease (GVHD) in a mismatched mouse model. We have extended these findings to reveal that B cell depletion of the donor graft results in more rapid T cell engraftment and higher IL-2, IFN-γ and TNF-α production by engrafting alloagressive T cells. In turn the degree of cytokine production was highly correlated with the degree of weight loss in mice developing GVHD underscoring the importance of T cell derived inflammatory cytokines in the development of GVHD. Conversely, those mice treated with additional resting B cells at the time of marrow infusion showed lower levels of cytokine production from engrafting T cells and subsequently less GVHD. Further, the amount of INF-γ and TNF-α production from alloaggressive T cells post transplant was substantially greater when a donor splenocytes we used to supplement bone marrow. The clinical score and histological examination of mice undergoing splenocyte + bone marrow transplant showed substantially differences compared to that observed in the bone marrow only model The post splenocyte transplant model reflected a hyperacute GVHD syndrome as opposed to clinically relevant, histologically proven acute GVHD derived from the transplant of bone marrow and furhet indicate that rapid disregulated T cells engraftmnet of central to the onset of devastaing GVHD. These findings indicate that resting B cells may regulate T cell engraftment and activation through regulating T cell homeostasis and suppression of inflammatory cytokines. B cells therefore may potentially be used therapeutically to limit GVHD mediated by alloaggressive T cells, whilst profound pre-transplant depletion of B cells may be detrimental to transplant outcome due to the promotion of GVHD.

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