• Title/Summary/Keyword: type 1 T cells

Search Result 627, Processing Time 0.028 seconds

Natural Killer and CD8 T Cells Contribute to Protection by Formalin Inactivated Respiratory Syncytial Virus Vaccination under a CD4-Deficient Condition

  • Eun-Ju Ko;Youri Lee;Young-Tae Lee;Hye Suk Hwang;Yoonsuh Park;Ki-Hye Kim;Sang-Moo Kang
    • IMMUNE NETWORK
    • /
    • v.20 no.6
    • /
    • pp.51.1-51.17
    • /
    • 2020
  • Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.

Lupeol Improves TNF-α Induced Insulin Resistance by Downregulating the Serine Phosphorylation of Insulin Receptor Substrate 1 in 3T3-L1 Adipocytes (3T3-L1 지방세포에서 루페올의 IRS-1의 인산화 조절을 통한 TNF-α 유도 인슐린 저항성 개선 효과)

  • Hyun Ah Lee;Ji Sook Han
    • Journal of Life Science
    • /
    • v.33 no.11
    • /
    • pp.859-867
    • /
    • 2023
  • Lupeol is a type of pentacyclic triterpene that has been reported to have therapeutic effects for treating many diseases; however, its effect on insulin resistance is unclear clear. This study examined the inhibitory effect of lupeol on the serine phosphorylation of insulin receptor substrate-1 in insulin resistance-induced 3T3-L1 adipocytes. 3T3-L1 cells were cultured and treated with tumor necrosis factor-α (TNF-α) for 24 hours to induce insulin resistance. Cells treated with different concentrations of lupeol (15 μM or 30 μM) or 100 nM of rosiglitazone were incubated. Then, lysed cells underwent western blotting. Lupeol exhibited a positive effect on the negative regulator of insulin signaling and inflammation-activated protein kinase caused by TNF-α in adipocytes. Lupeol inhibited the activation of protein tyrosine phosphatase-1B (PTP-1B)-a negative regulator of insulin signaling-and c-Jun N-terminal kinase (JNK); it was also an inhibitor of nuclear factor kappa-B kinase (IKK) and inflammation-activated protein kinases. In addition, Lupeol downregulated serine phosphorylation and upregulated tyrosine phosphorylation in insulin receptor substrate-1. Then, the downregulated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway was activated, the translocation of glucose transporter type 4 was stimulated to the cell membrane, and intracellular glucose uptake increased in the insulin resistance-induced 3T3-L1 adipocytes. Lupeol may improve TNF-α-induced insulin resistance by downregulating the serine phosphorylation of insulin receptor substrate 1 by inhibiting negative regulators of insulin signaling and inflammation-activated protein kinases in 3T3-L1 adipocytes.

Signal Transduction of C-Terminal Phosphorylation Regions for Equine Luteinizing Hormone/Chorionic Gonadotropin Receptor (eLH/CGR)

  • Byambaragchaa, Munkhzaya;Joo, Hyo-Eun;Kim, Sang-Gwon;Kim, Yean-Ji;Park, Gyeong-Eun;Min, Kwan-Sik
    • Development and Reproduction
    • /
    • v.26 no.1
    • /
    • pp.1-12
    • /
    • 2022
  • This study aimed to investigate the signal transduction of phosphorylation sites at the carboxyl (C)-terminal region of equine luteinizing hormone/chorionic gonadotropin receptor (eLH/CGR). The eLH/CGR has a large extracellular domain of glycoprotein hormone receptors within the G protein-coupled receptors. We constructed a mutant (eLH/CGR-t656) of eLH/CGR, in which the C-terminal cytoplasmic tail was truncated at the Phe656 residue, through polymerase chain reaction. The eLH/CGR-t656 removed 14 potential phosphorylation sites in the intracellular C-terminal region. The plasmids were transfected into Chinese hamster ovary (CHO)-K1 and PathHunter Parental cells expressing β-arrestin, and agonist-induced cAMP responsiveness was analyzed. In CHO-K1 cells, those expressing eLH/CGR-t656 were lower than those expressing eLH/CGR wild-type (eLH/CGR-wt). The EC50 of the eLH/CGR-t656 mutant was approximately 72.2% of the expression observed in eLH/CGR-wt. The maximal response in eLH/CGR-t656 also decreased to approximately 43% of that observed in eLH/CGR-wt. However, in PathHunter Parental cells, cAMP activity and maximal response of the eLH/CGR-t656 mutant were approximately 173.5% and 100.8%, respectively, of that of eLH/CGR-wt. These results provide evidence that the signal transduction of C-terminal phosphorylation in eLH/CGR plays a pivotal role in CHO-K1 cells. The cAMP level was recovered in PathHunter Parental cells expressing β-arrestin. We suggest that the signal transduction of the C-terminal region phosphorylation sites is remarkably different depending on the cells expressing β-arrestin in CHO-K1 cells.

Effects of Phytol and Small Water Dropwort Extract on the T Subset in the Sarcoma 180-Transplanted Mice (Phytol과 들미나리추출물이 Sarcoma 180마우스의 T Subset에 미치는 효과)

  • 김광혁;장명웅;박건영;이숙희;류태형;선우양일
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.22 no.4
    • /
    • pp.405-411
    • /
    • 1993
  • Several studies have shown that phytol isolated from perilla leaf and small water dropwort (Oenanthe javanica (BL) D.C., wild type) extract reveal antirumor activities. In the present study we investigated the effect of phytol and the small water dropwort extract on the T subset in the sarcoma 180-transplanted mice in order to elucidate the immunological mechanism of antiturmor activity of these substances. The results obtained from the experiment were as follows : When phytol was injected into the sarcoma-180 transplanted mice (control), the levels of T cell and T subset by inoculation of the tumor cells were enhanced, but that of T cells in case of small water dropwort extract was similar to the control. Asialo GM1$^{+}$ cells were increased when phytol or small water dropwort extract with injected into tumor-transplanted mice. In normal mice the number of asialo GM1$^{+}$ cells increased with phytol injection and decreased with small water dropwort extract injection. L3T4$^{+}$/Lyt-2$^{+}$cell ratios were decreased when phytol was injected into tumor-transplanted mire, but increased in case of small water dropwort extract injection. In normal mice the ratios showed large decreases with phytol or small water dropwort extract injection. These results indicate that phytol or small water dropwort extract ran activate the proliferation of natural killer cells that are effector cells in tumor-bearing mice.

  • PDF

Effect of King Oyster Mushroom (Pleurotus eryngii) Extracts on the Activation of Spleen Cells and Macrophage in Mice (새송이버섯 열수 추출물이 마우스 비장세포와 대식세포의 활성에 미치는 효과)

  • Kim, Kyoung-Ok;Ryu, Hye-Sook
    • The Korean Journal of Food And Nutrition
    • /
    • v.30 no.3
    • /
    • pp.525-530
    • /
    • 2017
  • King oyster mushroom (Pleurotus eryngii), an improved species of oyster mushroom, is a popular ingredient in Asian cuisine. Spleen cells were treated with various concentrations (0, 5, 10, 50, 100, 250, 500, and $1,000{\mu}g/mL$) of king oyster water extracts (KOWE); then, the proliferation of the cells was measured 24, 48, and 72 h after each treatment. Also, type 1 T helper cytokine productions ($TNF-{\alpha}$, $IFN-{\gamma}$, and IL-2) were measured in activated macrophage by KOWE in seven concentrations. Under the condition of its 50, 100, 250, and $1,000{\mu}g/mL$ for 48 h, the proliferation of cells was increased. However, there was no significant fluctuation in the spleen cells proliferation for 24 and 72 h-long KOWE exposure. To determine cytokine ($TNF-{\alpha}$, $IFN-{\gamma}$, IL-2) productions of type 1 T helper cells, macrophage was stimulated by KOWE for 48 h. Treatment of KOWE gave a rise to the levels of $TNF-{\alpha}$ and $IFN-{\gamma}$, but not in that of IL-2 productions. These results suggest that king oyster mushroom water extracts may be beneficial for enhancing immune functions in its high concentration.

Proteasome Function Is Inhibited by Polyglutamine-expanded Ataxin-1, the SCA1 Gene Product

  • Park, Yongjae;Hong, Sunghoi;Kim, Sung-Jo;Kang, Seongman
    • Molecules and Cells
    • /
    • v.19 no.1
    • /
    • pp.23-30
    • /
    • 2005
  • Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder caused by expansion of the polyglutamine tract in the SCA1 gene product, ataxin-1. Using d2EGFP, a short-lived enhanced green fluorescent protein, we investigated whether polyglutamine-expanded ataxin-1 affects the function of the proteasome, a cellular multicatalytic protease that degrades most misfolded proteins and regulatory proteins. In Western blot analysis and immunofluorescence experiments, d2EGFP was less degraded in HEK 293T cells transfected with ataxin-1(82Q) than in cells transfected with lacZ or empty vector controls. To test whether the stability of the d2EGFP protein was due to aggregation of ataxin-1, we constructed a plasmid carrying $ataxin-1-{\Delta}114$, lacking the self-association region (SAR), and examined degradation of the d2EGFP. Both the level of $ataxin-1-{\Delta}114$ aggregates and the amount of d2EGFP were drastically reduced in cells containing $ataxin-1-{\Delta}114$. Furthermore, d2EGFP localization experiments showed that polyglutamine-expanded ataxin-1 inhibited the general function of the proteasome activity. Taken together, these results demonstrate that polyglutamine-expanded ataxin-1 decreases the activity of the proteasome, implying that a disturbance in the ubiquitin-proteasome pathway is directly involved in the development of spinocerebellar ataxia type1.

Resveratrol Suppresses CD4+ T Cell Activation and Differentiation in vitro (Resveratrol의 CD4+ T 세포 활성과 분화 억제 효과)

  • Seo, Dong-Won;Yi, Young-Joo;Lee, Sang-Myeong
    • Korean Journal of Plant Resources
    • /
    • v.27 no.5
    • /
    • pp.567-575
    • /
    • 2014
  • Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

GLOBAL STABILITY OF THE VIRAL DYNAMICS WITH CROWLEY-MARTIN FUNCTIONAL RESPONSE

  • Zhou, Xueyong;Cui, Jingan
    • Bulletin of the Korean Mathematical Society
    • /
    • v.48 no.3
    • /
    • pp.555-574
    • /
    • 2011
  • It is well known that the mathematical models provide very important information for the research of human immunodeciency virus type. However, the infection rate of almost all mathematical models is linear. The linearity shows the simple interaction between the T-cells and the viral particles. In this paper, a differential equation model of HIV infection of $CD4^+$ T-cells with Crowley-Martin function response is studied. We prove that if the basic reproduction number $R_0$ < 1, the HIV infection is cleared from the T-cell population and the disease dies out; if $R_0$ > 1, the HIV infection persists in the host. We find that the chronic disease steady state is globally asymptotically stable if $R_0$ > 1. Numerical simulations are presented to illustrate the results.

Metabolite analysis in the type 1 diabetic mouse model

  • Park, Sung Jean
    • Journal of the Korean Magnetic Resonance Society
    • /
    • v.25 no.3
    • /
    • pp.33-38
    • /
    • 2021
  • Type 1 diabetes mellitus (T1DM) is caused by insufficient production of insulin, which is involved in carbohydrate metabolism. Type 2 diabetes mellitus (T2DM) has insulin resistance in which cells do not respond adequately to insulin. The purpose of this study was to estimate the characteristics of type 1 diabetes using streptozotocin-treated mice (STZ-mouse). The sera samples were collected from the models of hyperglycemic mouse and healthy mouse. Based on the pair-wise comparison, five metabolites were found to be noticeable: glucose, malonic acid, 3-hyroxybutyrate, methanol, and tryptophan. It was very natural glucose was upregulated in STZ-mouse. 3-hyroxybutyrate was also increased in the model. However, malonic acid, tryptophan, and methanol was downregulated in STZ-mouse. Several metabolites acetoacetate, acetone, alanine, arginine, asparagine, histidine, lysine, malate, methionine, ornithine, proline, propylene glycol, threonine, tyrosine, and urea tended to be varied in STZ-mouse while the statistical significance was not stratified for the variation. The multivariate model of PCA clearly showed the group separation between healthy control and STZ-mouse. The most significant metabolites that contributed the group separation included glucose, citrate, ascorbate, and lactate. Lactate did not show the statistical significance of change in t-test while it tends to down-regulated both in DNP and Diabetes.

Suppressive Effects of GHS in Knee Joint, Regional Lymph Nodes, and Spleen on Collagen-induced Arthritis in Mice (Collagen II로 유도된 CIA 관절염 생쥐의 대한 가미해동피산(加味海桐皮散)의 억제 효과)

  • Kim, Nam-Uk;Kim, Dong-Hui
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.21 no.5
    • /
    • pp.1233-1242
    • /
    • 2007
  • Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which might be mediated by the altered activation of Immune system, ultimately leading to the destruction of cartilage and bone. To examine effects of GHS on rheumatoid arthritis DBA/1J mice were immunized with bovine type II collagen to induced arthritis and then treated with GHS once a day for 7 weeks. Oral administration of GHS (200 mg/Kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/Kg), a positive control. The severity of arthritis within the knee joints, which was evaluated by histological assessment of cartilage destruction and pannus formation, was also lowered by GHS. The production of TNF-and IL-6 in serum was significantly suppressed. The levels of IFN-g in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. The levels of IgG and IgM RA factor were also decreased in the serum. FACS analysis indicated that B cells (in DLN), CD3+ T cells (in spleen, and paw joint), CD11b+Gr-1+ cells (in paw joint), CD3+CD49b(DX5) (in PBMC) were decreased and there was increased proportion of CD3+, CD4+, CD8+, CD4+CD25+ T cells in DLN. In conclusion, our results demonstrates that GHS significantly suppressed the progression of CIA and this action was characterized by the decreased production of TNF-a, IL-6, and rheumatoid factors, and modulations of immune cell populations.