Biomedical subjects

Seung-Woo Lee

Publications and source records attributed to Seung-Woo Lee.

10 recordsLinked to original sources

PubMed2006

Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell responses.

Members of the TNFR family are thought to deliver costimulatory signals to T cells and modulate their function and survival. In this study, we compare the role of two closely related TNFR family molecules, OX40 and 4-1BB, in generating effector CD8 T cells to Ag delivered by adenovirus. OX40 and 4-1BB were both induced on responding naive CD8 T cells, but 4-1BB exhibited faster and more sustained kinetics than OX40. OX40-deficient CD8 T cells initially expanded normally; however, their accumulation and survival at late times in the primary response was significantly impaired. In contrast, 4-1BB-deficient CD8 T cells displayed hyperresponsiveness, expanding more than wild-type cells. The 4-1BB-deficient CD8 T cells also showed enhanced maturation attributes, whereas OX40-deficient CD8 T cells had multiple defects in the expression of effector cell surface markers, the synthesis of cytokines, and in cytotoxic activity. These results suggest that, in contrast to current ideas, OX40 and 4-1BB can have a clear functional dichotomy in modulating effector CD8 T cell responses. OX40 can positively regulate effector function and late accumulation/survival, whereas 4-1BB can initially operate in a negative manner to limit primary CD8 responses.

Adenoviridae↗

PubMed2006

Design of highly efficient receptor sites by combination of cyclodextrin units and molecular cavity in TiO2 ultrathin layer.

A highly effective approach was developed for sensitive detection of organic substances in water. In order to achieve high sensitivity and selective detection for aromatic compounds, cyclodextrin (CD) hosts and imprinting effects were combined to fabricate binding sites within TiO(2) ultrathin layer. The electrode surface was modified with ultrathin TiO(2) gel film containing a 2:1 complex of beta-CD and bisphenol A (BPA), and then the BPA moiety was removed by washing. The resulting BPA-imprinted TiO(2)/beta-CD film showed specific and sensitive detection of BPA, as confirmed by quartz crystal microbalance (QCM) and cyclic surface-polarization impedance (cSPI) measurements. The high selectivity for BPA relative to structurally related guest molecules was estimated to be 1.6-3.4 at the guest concentration of 2x10(-7)M, and was considered to arise from the synergic effect of the binding site.

Benzhydryl Compounds↗

PubMed2006

Tumor necrosis factor/tumor necrosis factor receptor family members that positively regulate immunity.

The interactions between members of the tumor necrosis factor (TNF) family and their specific receptors (TNFRs) are influential in controlling cell division, life, and death. Recent evidence suggests that these interactions control the functionality and longevity of many types of cells involved in immune responses. In particular, it has become evident that certain interactions support the clonal expansion and survival of T-cells, B-cells, and dendritic cells and thus are essential for establishing a robust immune response. This review describes select TNF/TNFR family members that principally support activation and survival and prevent excessive cell death of T-cells (OX40L/OX40, 4-1BBL/4-1BB, CD30L/CD30, LIGHT/HVEM, CD70/CD27, and GITRL/GITR), B-cells (BAFF/BAFFR), and dendritic cells (RANKL/RANK). Expression of these ligands and receptors on the cell surface is highly regulated, and communication via them occurs during contact between T-cells and dendritic cells and between T-cells and B-cells. The functional dynamic between these TNF/TNFR members is slowly being unraveled, including whether these molecules act together or sequentially or control different type of immune responses. This review summarizes aspects of these TNF/TNFR interactions that are potentially important to immune responses.

Animals↗

PubMed2005

Magnetically agitated photocatalytic reactor for photocatalytic oxidation of aqueous phase organic pollutants.

A magnetically agitated photocatalytic reactor (MAPR) has been developed and assessed for oxidation of phenol. The MAPR uses a titanium dioxide composite photocatalyst with a ferromagnetic barium ferrite core. The catalyst motion was controlled with a dual-component magnetic field. First, a permanent magnet above the reactor provided a static magnetic field to counteract the force of gravity, hence increasing catalyst exposure to UV. Second, an alternating magnetic field generated by a solenoid was used to agitate the catalyst, thus increasing mass transfer between pollutants and byproducts to the catalyst. Optimal performance of the MAPR was achieved with the permanent magnet present and 1 A of alternating current to the solenoid between 20 and 80 Hz. Operating with a 60-Hz signal at 1 A with the permanent magnet present and 100 mg of catalyst, the system reduced an 11 mg/L phenol concentration by97% and decreased nonpurgeable dissolved organic carbon by 93% in 7 h using three 8-W 365-nm peak UV lamps.

Catalysis↗

PubMed2005

Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor.

Mast cells are the major effector-cell type for immediate hypersensitivity and other forms of allergic reactions. Expression of 4-1BB, a member of the tumor necrosis factor receptor superfamily, is induced at mRNA and protein levels on stimulation through the high-affinity receptor for immunoglobulin E (IgE; FcepsilonRI). In this study, we present evidence that agonistic anti-4-1BB antibodies can enhance FcepsilonRI-induced cytokine production and secretion. Consistent with this, 4-1BB-deficient mast cells exhibit reduced degranulation and cytokine production on FcepsilonRI stimulation. Analysis of 4-1BB ligand (4-1BBL)-deficient cells supported this notion. As a potential mechanism for these defects, we identified a defect in Ca2+ flux induced by FcepsilonRI stimulation. The defective Ca2+ flux could be accounted for by the reduced activity of Lyn/Btk/phospholipase C-gamma2 pathway and constitutive interactions between 4-1BB and Lyn. Therefore, FcepsilonRI-inducible 4-1BB plays a costimulatory function together with FcepsilonRI stimulation.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2005

Enhanced CD4 T cell responsiveness in the absence of 4-1BB.

The 4-1BB (CD137) is a member of the TNFR superfamily, and is expressed on several cell types, including activated T cells. Although 4-1BB ligation by agonistic Ab or 4-1BB ligand-expressing APCs can costimulate T cells, the physiological significance of 4-1BB expression in vivo during T cell responses is still being elucidated. In this study, we have addressed the impact on CD4 T cell priming when 4-1BB is absent after gene targeting. Surprisingly, 4-1BB(-/-) mice generated more enhanced effector CD4 T cell responses to OVA protein in adjuvant, even though Ab responses in 4-1BB(-/-) mice were normal. Using an adoptive transfer system with OT-II TCR transgenic CD4 T cells, we found that 4-1BB(-/-) CD4 cells responding in a 4-1BB-sufficient environment had enhanced cell division compared with wild-type cells and displayed augmented clonal expansion during the primary response. This was not due to a developmental defect as 4-1BB-deficient CD4 cells could respond normally to Ag in vitro. These results demonstrate that the absence of 4-1BB can make CD4 T cells hyperresponsive to protein Ag in vivo, suggesting a new unappreciated negative regulatory role of 4-1BB when expressed on a T cell.

Adjuvants, Immunologic↗

PubMed2005

The effect of dimyristoylphosphatidylethanol on the lateral and rotational mobilities of liposome lipid bilayers.

The aim of this study was to provide the basis to further examine the mode of action of ethanol. Fluorescent probes reported to have different membrane mobilities were used to evaluate the effect of dimyristoylphosphatidylethanol (DMPEt) on the lateral and rotational mobilities of liposome lipid bilayers. An experimental procedure, based on the selective quenching of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, was used. DMPEt increased the bulk lateral and rotational mobilities, and had a greater fluidizing effect on the outer than the inner monolayer. These effects of DMPEt on liposomes may be responsible for some, but not all, of the general anesthetic actions of ethanol.

Animals↗

PubMed2004

IL-12 priming during in vitro antigenic stimulation changes properties of CD8 T cells and increases generation of effector and memory cells.

Antigenic and costimulatory signals trigger a developmental program by which naive CD8 T cells differentiate into effector and memory cells. However, initial cytokine signals that regulate the generation of effector and memory CD8 T cells are not well understood. In this study, we show that IL-12 priming during in vitro antigenic stimulation results in the significant increase of both primary and memory CD8 T cell population in mice after adoptive transfer of activated cells. The effect of IL-12 priming is closely associated with qualitative changes in CD8 T cells, such as reduced MHC I tetramer binding and CD69 expression, altered distribution of lipid rafts, decreased cytolytic activity, and less susceptibility to apoptosis. Furthermore, exogenous IL-12 priming improved the intrinsic survival properties of memory CD8 T cells, leading to better protective immunity and vaccine-induced memory CD8 T cell responses. However, the experiments with IL-12p40- and IL-12Rbeta1-deficient mice showed similar levels of primary and memory CD8 T cell responses compared with wild-type mice, implying that endogenous IL-12 and/or IL-12R signaling in vivo is not critical for CD8 T cell immunity. Together, our results suggest that IL-12 can serve as an important, but dispensable regulatory factor for the development of CD8 T cells, and IL-12 priming could be useful in many medical applications.

Adoptive Transfer↗

PubMed2004

Rod-like architecture and helicity of the poly(C)/schizophyllan complex observed by AFM and SEM.

Microscopic studies of the complex between poly(C) and schizophyllan (SPG), employing both AFM and SEM, revealed that the complex takes the same rod-like architecture on the mica surface as those of the renatured SPG and the original triple helix of SPG, indicating that the complex also has a helical structure. The SEM observations showed the helical pattern on the rod surface, only when the sample was metal shadowed. The pitch evaluated from the image is comparable with that obtained from crystallographic data. The ability to visualize the helical structure can be explained from the hypothesis that the platinum grains may assemble on the sample using the molecular surface of the SPG (or complex) as the template.

Carbohydrate Conformation↗

PubMed2004

Effects of dopamine HCl on structural parameters of bovine brain membranes.

Fluorescence probes located in different membrane regions were used to evaluate the effect of dopamine.HCl on the structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and thickness of the lipid bilayer) of synaptosomal plasma membrane vesicles (SPMV), which were obtained from the bovine cerebral cortex. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, and radiationless energy transfer from the tryptophan of membrane proteins to Py-3-Py and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS) was also utilized. Dopamine.HCl increased both the bulk lateral mobility and annular lipid fluidity, and it had a greater fluidizing effect on the inner monolayer than on the outer monolayer. Furthermore, the drug had a clustering effect on membrane proteins.

Anilino Naphthalenesulfonates↗