scholarly journals Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3120
Author(s):  
Jae Jeon ◽  
Byung-Cheol Lee ◽  
Doman Kim ◽  
Daeho Cho ◽  
Tae Kim
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Water Soluble ◽  
Th1 Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Th1 Cell ◽  
Ifn Γ

A flavonoid Astragalin (kaempferol-3-O-β-d-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O-β-d-isomaltotrioside, Ast-Gal) on murine bone marrow-derived dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through the upregulation of surface markers, such as cluster of differentiation (CD)80, CD86, and Major histocompatibility complex (MHC) II in a dose-dependent manner, while Ast had little effects. Additionally, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as interleukin (IL)-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 monoclonal antibody (mAb) to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly decreased interferon (IFN)-γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

scholarly journals Hydrophilic Astragalin Galactoside Induces T Helper Type 1-Mediated Immune Responses via Dendritic Cells

2018 ◽  
Author(s):  
Jae Hyoung Jeon ◽  
Byung-Cheol Lee ◽  
Doman Kim ◽  
Daeho Cho ◽  
Tae Sung Kim
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Water Soluble ◽  
Th1 Cells ◽  
Dependent Manner ◽  
T Helper ◽  
Th1 Cell ◽  
Ifn Γ

A flavonoid Astragalin (kaempferol-3-O-β-D-glucopyranoside, Ast) has several biological activities including anti-oxidant, anti-HIV, and anti-allergic effects. Nonetheless, its insolubility in hydrophilic solvents imposes restrictions on its therapeutic applications. In this study, we investigated the effects of water-soluble astragalin-galactoside (kaempferol-3-O- β-D-isomaltotrioside, Ast-Gal) on dendritic cell (DC) maturation and T helper (Th) cell-mediated immune responses. Ast-Gal significantly increased maturation and activation of DCs through up-regulation of surface markers, such as CD80, CD86, and MHC II in a dose-dependent manner, while Ast had little effects. Also, Ast-Gal-treated DCs markedly secreted immune-stimulating cytokines such as IL-1β, IL-6, and IL-12. Importantly, Ast-Gal strongly increased expression of IL-12, a polarizing cytokine of Th1 cells. In a co-culture system of DCs and CD4+ T cells, Ast-Gal-treated DCs preferentially differentiates naïve CD4+ T cells into Th1 cells. The addition of neutralizing IL-12 mAb to cultures of Ast-Gal-treated DCs and CD4+ T cells significantly increased IFN- γ production, thereby indicating that Ast-Gal-stimulated DCs enhance the Th1 response through IL-12 production by DCs. Injection with Ast-Gal-treated DCs in mice increased IFN-γ-secreting Th1 cell population. Collectively, these findings indicate that hydrophilically modified astragalin can enhance Th1-mediated immune responses via DCs, and point to a possible application of water-soluble astragalin-galactoside as an immune adjuvant.

scholarly journals Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.

1996 ◽  
Vol 184 (2) ◽  
pp. 473-483 ◽  
Author(s):  
T Sornasse ◽  
P V Larenas ◽  
K A Davis ◽  
J E de Vries ◽  
H Yssel
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Th2 Cells ◽  
Cell Phenotype ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th1 And Th2

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.

scholarly journals Immune response evaluation in Balb/c mice after crude extract of Anisakis typica sensitization

2019 ◽  
Vol 12 (10) ◽  
pp. 1529-1534
Author(s):  
Linda Haryadi ◽  
Eddy Suprayitno ◽  
Aulanni'am Aulanni'am ◽  
Anik Martinah Hariati
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Crude Extract ◽  
Cd4 T Cells ◽  
Classical Model ◽  
Economic Value ◽  
Dependent Manner ◽  
T Helper ◽  
Food Antigens ◽  
Ifn Γ

Background and Aim: Anisakis is a global challenge for a fish product which may lead to a decrease in economic value and consumers' preference. Skipjack (Katsuwonus pelamis) in Kupang, Nusa Tenggara Timur, Indonesia, have important economic value for local fisheries. Anisakis typica is one of the Anisakis species which potent to induce an allergic reaction. However, the study about A. typica involved in the dendritic cells (DCs), T helper 1 (Th1), T helper 2 (Th2), and regulatory T cells (Tregs) is still limited. This study aimed to analyze the dynamic changed of the immune system including DCs, CD4+ T cells, and Tregs after 1 week of A. typica sensitization. Materials and Methods: Twenty-four male Balb/C mice were randomly divided into four groups (n=6), mice treated with crude A. typica extract (CAE) 50, 75, and 100 mg/kg BW, respectively. CAE was given orally per day for a week. At the end of the experiment, the animals were sacrificed and the spleen was collected. DCs were labeled as CD11c+ interleukin-6+ (IL-6+); CD4+ T cells were distinguished as Th1 (CD4+ interferon-γ+ [IFN-γ+]) and Th2 (CD4+ IL-4+ and CD4+ IL-5+); Tregs were labeled as CD4+CD25+CD62L+. The expression of each cell was determined by flow cytometry. Results: Our result described that CAE elicits CD11c+ IL-6+, CD4+ IFN-γ+, CD4+ IL-4+, and CD4+ IL-5+ and reduces CD4+CD25+CD62L+ significantly (p<0.05) in dose-dependent manner in mice after A. typica infection. Conclusion: The Th1/Th2 ratio after A. typica crude extract treatment exhibits a mixed pattern rather than the classical model allergy to food antigens. Our study is expected as a basic understanding of the changes in immune response after A. typica infection.

scholarly journals T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor β2 Chain Expression and Signaling

2000 ◽  
Vol 191 (5) ◽  
pp. 847-858 ◽  
Author(s):  
Ryuta Nishikomori ◽  
Rolf O. Ehrhardt ◽  
Warren Strober
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
Th1 Cells ◽  
T Helper ◽  
Ifn Γ ◽  
Helper Type

The differentiation of CD4+ T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor β2 (IL-12Rβ2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rβ2 chain. We reexamined such differentiation using IL-12Rβ2 chain transgenic mice. We found that CD4+ T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-γ production 10–100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rβ2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rβ2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4–driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-γ production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.

scholarly journals Interferon γ Signaling Alters the Function of T Helper Type 1 Cells

2000 ◽  
Vol 192 (7) ◽  
pp. 977-986 ◽  
Author(s):  
Gregory Z. Tau ◽  
Thierry von der Weid ◽  
Binfeng Lu ◽  
Simone Cowan ◽  
Marina Kvatyuk ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Leishmania Major ◽  
Interferon Γ ◽  
Delayed Type Hypersensitivity ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Ifn Γ ◽  
And Function

One mechanism regulating the ability of different subsets of T helper (Th) cells to respond to cytokines is the differential expression of cytokine receptors. For example, Th2 cells express both chains of the interferon γ receptor (IFN-γR), whereas Th1 cells do not express the second chain of the IFN-γR (IFN-γR2) and are therefore unresponsive to IFN-γ. To determine whether the regulation of IFN-γR2 expression, and therefore IFN-γ responsiveness, is important for the differentiation of naive CD4+ T cells into Th1 cells or for Th1 effector function, we generated mice in which transgenic (TG) expression of IFN-γR2 is controlled by the CD2 promoter and enhancer. CD4+ T cells from IFN-γR2 TG mice exhibit impaired Th1 polarization potential in vitro. TG mice also display several defects in Th1-dependent immunity in vivo, including attenuated delayed-type hypersensitivity responses and decreased antigen-specific IFN-γ production. In addition, TG mice mount impaired Th1 responses against Leishmania major, as manifested by increased parasitemia and more severe lesions than their wild-type littermates. Together, these data suggest that the sustained expression of IFN-γR2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-γ–unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.

scholarly journals Dexmedetomidine Directs T Helper Cells toward Th1 Cell Differentiation via the STAT1-T-Bet Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Daoyun Lei ◽  
Li Liu ◽  
Songhui Xie ◽  
Haiyan Ji ◽  
Yanxing Guo ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Subset ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
Th1 Cell ◽  
Adrenergic Antagonist ◽  
Ifn Γ

Dexmedetomidine is an α2 adrenergic receptor agonist that has been reported to modulate the polarization of CD4+ T cells. However, the underlying mechanisms by which dexmedetomidine induces T-helper 1 (Th1) cell differentiation remain poorly understood. The aim of this study was to explore the potential mechanisms through which dexmedetomidine can induce Th1 cell differentiation. Purified CD4+ T cells were stimulated with anti-CD3/anti-CD28 and then treated with dexmedetomidine. Flow cytometry analysis was adopted to measure the concentration of Th1 cells. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qPCR) were performed to detect protein levels and mRNA expression, respectively, of IFN-γ and IL-4. Western blotting was used to determine the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and T-bet expression. The Th1 cell subset and IFN-γ levels were elevated in the dexmedetomidine-induced CD4+ T cells. Dexmedetomidine enhanced the phosphorylation of STAT1 and the expression of T-bet in the CD4+ T cells. Atipamezole (an α2 adrenergic antagonist) and fludarabine (a STAT1 inhibitor) reversed the dexmedetomidine-induced Th1 cell differentiation. These results suggested that dexmedetomidine induced Th1 cell differentiation via the STAT1-T-bet signaling pathway.

scholarly journals The effect of Kefir on The Immune Response of Healthy Volunteers In Vitro

2017 ◽  
Vol 3 (2) ◽  
pp. 28
Author(s):  
Desie Dwi Wisudanti
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Fermented Milk ◽  
Bioactive Components ◽  
Ifn Γ

Kefir is a functional foodstuff of probiotics, made from fermented milk with kefir grains containing various types of beneficial bacteria and yeast. There have been many studies on the effects of oral kefir on the immune system, but few studies have shown the effect of bioactive components from kefir (peptides and exopolysaccharides/ kefiran), on immune responses. The purpose of this study was to prove the effect of kefir supernatant from milk goat on healthy immune volunteer response in vitro. The study was conducted on 15 healthy volunteers, then isolated PBMC from whole blood, then divided into 5 groups (K-, P1, P2, P3 and P4) before culture was done for 4 days. The harvested cells from culture were examined for the percentage of CD4+ T cells, CD8+ T cells, IFN-γ, IL-4 using flowsitometry and IL-2 levels, IL-10 using the ELISA method. The results obtained that kefir do not affect the percentage of CD4+ T cells and CD8+ T cells. The higher the concentration of kefir given, the higher levels of secreted IFN- γ and IL-4, but a decrease in IL-2 levels. Significant enhancement occurred at levels of IL-10 culture PBMC given kefir with various concentrations (p <0.01), especially at concentrations of 1%. These results also show the important effects of kefir bioactive components on immune responses. The conclusion of this study is that kefir can improve the immune response, through stimulation of IL-10 secretion in vitro.

Su.67. Monocytes Modulate T-Cell Immune Responses in a Pge2-Cox-2 Dependent Manner and Induce Foxp3+-Cd4+- T-Cells

2006 ◽  
Vol 119 ◽  
pp. S183
Author(s):  
Sheraz Yaqub ◽  
Tone Bryn ◽  
Milada Mahic ◽  
Einar Aandahl ◽  
Kjetil Tasken
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Dependent Manner ◽  
T Cell Immune Responses ◽  
Cox 2

scholarly journals IL-36 signaling amplifies Th1 responses by enhancing proliferation and Th1 polarization of naive CD4+ T cells

Blood ◽  
2012 ◽  
Vol 120 (17) ◽  
pp. 3478-3487 ◽  
Author(s):  
Solenne Vigne ◽  
Gaby Palmer ◽  
Praxedis Martin ◽  
Céline Lamacchia ◽  
Deborah Strebel ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Interleukin 1 ◽  
Th1 Cell ◽  
Critical Function ◽  
Mediators Of Inflammation ◽  
Th1 Polarization

AbstractThe interleukin-1 (IL-1) superfamily of cytokines comprises a set of pivotal mediators of inflammation. Among them, the action of IL-36 cytokines in immune responses has remained elusive. In a recent study, we demonstrated a direct effect of IL-36 on immune cells. Here we show that, among T cells, the IL-36 receptor is predominantly expressed on naive CD4+ T cells and that IL-36 cytokines act directly on naive T cells by enhancing both cell proliferation and IL-2 secretion. IL-36β acts in synergy with IL-12 to promote Th1 polarization and IL-36 signaling is also involved in mediating Th1 immune responses to Bacillus Calmette-Guerin infection in vivo. Our findings point toward a critical function of IL-36 in the priming of Th1 cell responses in vitro, and in adaptive immunity in a model of mycobacterial infection in vivo.

GATA-3 Requires C-Myb to Auto-Regulate Its Own Expression in Normal Human Peripheral Blood Lymphocytes Undergoing T Helper Type 2 (Th2) Cell Development

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2575-2575
Author(s):  
Yuji Nakata ◽  
Shenghao Jin ◽  
Yuan Shen ◽  
Alan M. Gewirtz
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Human Peripheral Blood ◽  
Cell Formation ◽  
Cell Development ◽  
Peripheral Blood Lymphocytes ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell

Abstract The c-myb protooncogene encodes a transcription factor, c-Myb, which is highly expressed in immature hematopoietic cells. c-Myb is required for many critical aspects of blood cell development including lineage fate selection, proliferation, and at multiple time points during early myeloid, and B and T lymphoid cell development. GATA-3, which belongs to a family of zinc finger transcription factors, is also required at several steps in early T cell development, and specifically in regard to this communication, for the development of T helper type 2 (Th2) cells. A recent study by Maurice et al (EMBO2007, 26:3629–3640) reported that c-myb regulates T helper cell lineage commitment in developing mouse thymocytes via regulation of GATA-3 expression. As we were unaware of any studies that have addressed the role of c-Myb and GATA-3 in normal human peripheral blood lymphocytes (PBL), we explored the potential regulatory relationship between these transcription factors in cells of this type. Proceeding from the murine studies, we performed a chromatin immunoprecipitation assay (ChIP) which showed that c-Myb bound the GATA-3 downstream promoter in naïve CD4+ T cells under conditions designed to promote Th2 growth. Such binding was not observed in cells stimulated under Th1 promoting conditions. The interaction of c-Myb and GATA-3 proteins was also detected in cell lysates under Th2 cell promoting conditions by immunoprecipitation with both anti-c-Myb, and anti-GATA-3 polyclonal antibodies. Of note, immunoprecipitation with these same antibodies did not show binding of either protein to STAT6. Additional studies revealed that c-Myb activated a GATA-3 minimal promoter by direct binding to a conserved c-Myb binding site in peripheral blood T cells. Of even greater interest, in 293T cells, GATA-3 activated its own promoter ~6 fold when c-Myb was co-expressed in 293T cells. In the absence of c-Myb, GATA-3 did not significantly activate its own promoter in these cells. We have recently shown that c-Myb binds to MLL via menin. A ChIP assay also showed that MLL and Menin bound to the GATA-3 promoter suggesting that c-Myb and GATA-3 form a co-activator complex on the GATA-3 promoter with MLL. Finally, to explore the role of c-myb expression in human peripheral blood naive CD4+ T cells, we employed c-Myb targeted, and control, short hairpin RNA (shRNA) expressed from a lentivirus vector. This strategy yielded a sequence specific 80–90% knockdown of c-Myb expression in our hands. Stimulation of naive peripheral blood CD4+ T cells expressing the c-Myb directed shRNA with cytokines promoting Th2 cell formation (IL-4, IL-2, and anti-IL-12 antibody) blocked the up-regulation of GATA-3 mRNA expression ~90% compared to cells in which a control shRNA had been expressed. Flow cytometric analysis revealed that intracellular IL-4 expression also was diminished. In contrast, silencing c-myb had no effect on T-bet mRNA expression, or intracellular interferon-expression in the cells induced to undergo Th1 cell formation with IL-12, IL-2 and anti-IL-4 antibody. We conclude from these studies that c-Myb regulates developmental programs specific for Th2, as opposed to Th1, cell development. We hypothesize that such control is exerted in peripheral blood T lymphocytes, at least in part, through direct control of GATA-3, whose expression is auto-regulated with the assistance of c-Myb, and perhaps MLL, acting as transcriptional co-factors.

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