Abstract 425: Lycopene Modulates T Lymphocyte Function by Modulating Th1 Responses and Treg Lymphocyte Population

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Lynsey M Mills ◽  
Heather Wilson ◽  
Frank Thies

Increased lycopene intake might have cardiovascular benefits, potentially through anti-inflammatory mechanisms. We recently showed that lycopene can influence lymphocyte activity by modulating processes involved in early cellular activation. T lymphocytes comprise different subsets, T cytotoxic, T helper 1 (Th1), T helper 2 (Th2) and T regulatory cells (Treg). We aimed to determine whether lycopene could specifically modulate T-cell subsets function and activity. Peripheral blood mononuclear cells from 11 healthy adults were cultured for 18hr to 60h in the presence of lycopene-enriched liposomes (0-1.18μg lycopene/ml) with or without mitogens. The secretion of cytokines representative of Th1,Th2 and Treg activities were measured by ELISA (IL-2, IL-1β, IL-10, IFN-γ and TGF-β) or cytometric bead array (IL-4, IL-10, IL17 and IFN-γ). The population profile of Tc (CD3+/CD8+), Th (CD3+/CD4+), Treg (CD4+/CD25+), and the Treg subsets nTreg (CD4+/CD25+/FoxP3+) and iTreg (CD4+/CD25+/IL-10+) was determined by flow cytometry. After 18h incubation, IL-2 concentration in the medium was significantly reduced (-29%, p=0.001) in the presence of lycopene (1.18μg/mL). Similar effects were observed after 36h and 60h culture for IFN-γ (-23%, p=0.015), Il-10 (-30%, p=0.023), IL-17 (-30%, p=0.019) but not IL-4 or TGF-β. The proportion of Treg cell was also significantly increased by 36% (p=0.001) in the presence of lycopene (1.18μg/mL) compared with non-treated activated cells. Furthermore, the proportions of iTreg cells were significantly increased by after incubation with lycopene while the proportion of nTreg cells decreased (-20.5 %, p=0.049). We conclude that increased lycopene intake may be beneficial against atherogenesis by modulating T lymphocyte function, particularly in relation toTh1 and Treg.

2002 ◽  
Vol 70 (3) ◽  
pp. 1301-1309 ◽  
Author(s):  
K. Robinson ◽  
K. R. Neal ◽  
C. Howard ◽  
J. Stockton ◽  
K. Atkinson ◽  
...  

ABSTRACT In order to study the immune response elicited by asymptomatic carriage of Neisseria meningitidis, samples of serum, peripheral blood mononuclear cells (PBMCs), and saliva were collected from a cohort of more than 200 undergraduate students in Nottingham, United Kingdom, who were subject to high rates of acquisition and carriage of meningococci. Serum immunoglobulin G levels were elevated following increases in the rate of carriage, and these responses were specific for the colonizing strains. In order to investigate T-cell responses, PBMCs from 15 individuals were stimulated with a whole-cell lysate of the H44/76 meningococcal strain (B:15:P1.7,16), stained to detect cell surface markers and intracellular cytokines, and examined by flow cytometry. The cells were analyzed for expression of CD69 (to indicate activation), gamma interferon (IFN-γ) (a representative T-helper 1 subset [Th1]-associated cytokine), and interleukin-5 (IL-5) (a Th2-associated cytokine). Following a brief meningococcal stimulation, the numbers of CD69+ IFN-γ+ CD56/16+ NK cells were much higher than cytokine-positive CD4+ events. Both IFN-γ+ and IL-5+ events were detected among the CD69+ CD4+ population, leading to the conclusion that an unbiased T-helper subset response was elicited by meningococcal carriage.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3873-3873
Author(s):  
Godfrey ChiFung Chan ◽  
W.K. Chan ◽  
H.K. Law ◽  
Z.B. Lin ◽  
Y.L. Lau

Abstract Background: Purified polysaccharides extracted from plants and fungi have been shown to induce immune responses in-vivo and vitro over the past decade. Currently, most of these polysaccharides are found to be glucan but with different branch structure and sizes. Their relative potency and effect on human immune cells remains unknown. This study aims to compare their relative effect on human dendritic cell, the most potent antigen presenting cell. Materials & Methods: We selected 2 prototypes of purified polysaccharides extracted from: 1) Ganoderma lucidum (GL, Lingzhi, Reishi) mycelium, a widely used herb with long and branching β (1® 3), (1® 6) glucan structure (provided by Prof. Lin ZB, Beijing) and 2) Barley with shorter and different branching β (1® 3), (1® 4) structure (provided by Prof. Cheung VNK, NY). Their characteristics and chemical properties had been reported previously. Human peripheral blood mononuclear cells (PBMCs) proliferation was studied by XTT assay. Human dendritic cells (DCs) were derived from monocytes and maturation of DCs were determined by: a) immunophenotypic shift using flow cytometer; 2) dextran endocytosis assay and 3) mixed lymphocytes reaction. Cytokine secretions were determined by ELISA test. Comparisons between means were by nonparametric Student’s t test (2-tailed). Results: We found that purified polysaccharides from GL but not barley could induce PBMCs proliferation and maturation of DCs. GL polysaccharides could enhance phenotypic and functional maturation of DCs with significant IL-12 and IL-10 production. DCs were relatively inert to Barley glucans stimulation. However, both polysaccharides did not polarize T cells into the direction of T helper 1, T helper 2 or regulatory T cells. Conclusions: Our study shown that purified polysaccharides extracted from plants and fungi have different effect on human DCs and their potency and effects are probably affected by their respective sources and structures.


2015 ◽  
Vol 6 (5) ◽  
pp. 697-705 ◽  
Author(s):  
Y.W. Liu ◽  
T.Y. Fu ◽  
W.S. Peng ◽  
Y.H. Chen ◽  
Y.M. Cao ◽  
...  

The efficacy of Lactobacillus paracasei V0151 (V0151), isolated from the faeces of a child, to modulate immune responses was investigated. In RAW 264.7 cells expressing an inducible nitric oxide synthase (iNOS)-directed luciferase gene, heat-inactivated V0151 stimulated iNOS expression followed by nitric oxide production. V0151 significantly elevated interferon gamma, interleukin (IL)-10, tumour necrosis factor alpha, and IL-1β production in human peripheral blood mononuclear cells. In splenocytes isolated from ovalbumin (OVA)-sensitised BALB/c mice treated with OVA and V0151 at different bacterium-to-cell ratios (1:1, 10:1, and 20:1) for 96 h, IL-2, IL-4, IL-5, and IL-13 production was dose-dependently downregulated, whereas IL-12 was dose-dependently upregulated. Collectively, our findings indicate that V0151 might regulate pro-inflammatory factors in macrophages and splenocytes. Furthermore, the T helper 1/T helper 2 (Th1/Th2) balance was also skewed toward Th1 dominance through the elevation of Th1 cytokine production.


1981 ◽  
Author(s):  
G A Levy ◽  
B S Schwartz ◽  
T S Edqinqton

Human peripheral blood mononuclear cells (PBM) in response to LPS stimulation generate increased quantities of thromboplastin activity. Monocytes are the cellular source of this activity and direct lymphocyte collaboration is required for its expression. PBM were separated by adherence into monocyte and lymphocyte fractions. Lymphocytes were further fractionated into T and non-T cells by rosetting with neuraminidase treated SRBC. 1 × 105 monocytes had a basal activity of 250 mU which increased to a maximum 2850 mU when monocytes were stimulated by 10 ug LPS for 6 hrs at a T cell: monocyte ratio of 4:1. No increase in thromboplastin activity was observed when monocytes were stimulated by LPS either alone or in the presence of non-T cells. Moretta et al. have described a system in which T cells are segregated into helper and suppressor subsets according to their ability to mediate immunoglobulin synthesis in response to pokeweed mitogen (PWM) stimulation. Using this system, T cells were further subfractionated into helper (Tμ), suppressor (Tγ ) and T null cells by cytoadherence to IgM or IgG coated ox RBC. 1 × 105 monocytes when incubated with increasing numbers of Tμ cells generated a maximal 4150 mU thromboplastin activity as the ratio of Tμ: monocytes approached 4:1. No increase in monocyte thromboplastin activity was observed above basal levels of 160 mU when monocytes were stimulated by LPS in the presence of either Tγ or T null cells. Tγ cells were observed to suppress Tμ helper cell function with a decrease in monocyte thromboplastin activity from 4150 mU to 1100 mU as the Tγ: Tμ ratio increased from 0:1 to 4:1. Thus, at least two populations within the T lymphocyte series the T μ (helper) and Tγ (suppressor) fractions modulate the expression of thromboplastin activity by monocytes.


2020 ◽  
Author(s):  
qiang shu ◽  
Jiao Sun ◽  
Yameng Sui ◽  
Yunqing Wang ◽  
Lijun Song ◽  
...  

Abstract Background: The calcineurin inhibitor tacrolimus (TAC) is the second-line treatment for rheumatoid arthritis (RA). Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA synovial tissues and synovial fluid. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and response to TAC in RA patients.Methods: Active RA patients were enrolled and treated with TAC alone or in combination with methotrexate and/or prednisone for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and at week 12. We measured Gal-9 expression in different subsets of peripheral blood mononuclear cells using flow cytometry and assayed Gal-9 levels in plasma. We also tested cytokine levels in plasma by ELISA. Results: The disease activity of RA patients notably decreased after TAC treatment. At baseline, the percentages of CD4+ T cells and T regulatory cells (CD4+CD25+CD127low) expressing Gal-9 were higher in the group with severe disease than in mild or moderate groups. After TAC treatment in RA patients, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8- cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets as well as lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients.Conclusion: Gal-9 can be regarded as a new biomarker for evaluating RA activity and efficacy of TAC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mi-Rae Shin ◽  
Ji Hye Lee ◽  
Jin A Lee ◽  
Min Ju Kim ◽  
Hae-Jin Park ◽  
...  

Abstract Background The present study extensively aimed to evaluate the underlying mechanism of the immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium (PLM). Methods To assess whether PLM influences the production of markers related to inflammation, Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with PLM (50, 100, 200, and 500 μg/mL). Splenocyte, thymus, peritoneal exudate cells (PEC), and peripheral blood mononuclear cells (PBMC) were isolated from the Balb/c mice treated with Korean red ginseng or PLM once a day for 5 weeks. Moreover, all mice except normal mice were stimulated with 10% proteose peptone (PP) treated 3 days before the sacrifice and 2% starch treated 2 days before the sacrifice. Subsequently, the cytotropic substance was evaluated by using flow cytometry analysis and ELISA assay. Results PLM200 treatment significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and inhibited the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α dose-dependently in the LPS-stimulated RAW264.7 cells. PLM200 supplementation showed a significant increase in IL-2, IL-12, and interferon (IFN)-γ production and upregulated the ratio of IFN-γ (T-helper type 1, Th1) to IL-4 (T-helper type 2, Th2) in splenocytes. After PLM200 treatment, the significant elevation of CD4+CD25+, CD4+&CD8+, and CD4+CD69+ treatment were detected in thymus. Moreover, CD4+ and CD4+CD69+ in PBMC and CD69+ in PEC were also shown in a significant increase. Conclusions Taken together, these results showed an immunomodulatory effect of PLM about an elevated INF-γ/IL4 ratio, as an index of Th1/Th2, as well as the anti-inflammatory effect in the LPS-stimulated RAW264.7 cells. Therefore, our findings demonstrate that PLM possesses immunostimulatory and anti-inflammatory effects.


2017 ◽  
Vol 15 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Chuanli Su ◽  
Tao Yang ◽  
Zhihong Wu ◽  
Jiang Zhong ◽  
Yunshu Huang ◽  
...  

The aim of this article is to study T-helper (Th) cell differentiation in the progression of acute, subacute, and chronic atopic dermatitis. Skin biopsies from 48 patients with acute, subacute, and chronic atopic dermatitis were studied using immunohistochemistry with antibodies to TARC/CCL17, CTACK/CCL27, and RANTES/CCL5. Peripheral blood mononuclear cells were studied in 17 patients using flow cytometry to measure the content of Th1/Th2 cells and Th17/Treg cells. Levels of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and transforming growth factor (TGF)-β1 were evaluated with enzyme-linked immunosorbent assay (ELISA). Distinctive expressions of T-cell-specific chemokines TARC/CCL17, CTACK/CCL27, and RANTES/CCL5 were observed at different stages of atopic dermatitis, which were consistent with the differentiation of the Th cell subsets, Th2/Th1, and Th17/Treg. Th2 and Th17 were acute-phase subsets, while Th1 and Treg were chronic-phase subsets. At an early stage of atopic dermatitis, Th17 and Th2 cells were found in peripheral blood mononuclear cells, followed by Th1 cells, Treg cells, and eosinophils; in late-stage or subacute and chronic atopic dermatitis, Th17 and Th2 cell numbers decreased. The levels of the IFN-γ and TGF-β1 increased during the progression of atopic dermatitis from acute to chronic forms. The levels of IL-17A and IL-4 decreased during the progression of atopic dermatitis from acute to chronic forms. The differentiation of Th subsets at distinct phases in atopic dermatitis may form the basis for further studies on the classification or control of this increasingly common clinical condition.


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