• Toxicological Research
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• v.29 no.2
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• pp.115-120
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• 2013

To investigate the effects of short-term exposure of beryllium on the human immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95, and NK cells, and the proportion of B cells and $TNF{\alpha}$ level in peripheral blood and immunoglobulins in the serum of 43 exposed workers and 34 healthy control subjects were studied. External exposure to beryllium was measured by atomic absorption spectrometer as recommended by the NIOSH analytical method 7300. T lymphocyte subpopulation analysis was carried out with flow cytometer. The working duration of exposed workers was less than 3 months and the mean ambient beryllium level was $3.4{\mu}g/m^3$, $112.3{\mu}g/m^3$, and $2.3{\mu}g/m^3$ in molding (furnace), deforming (grinding), and sorting processes, respectively (cited from Kim et al., 2008). However, ambient beryllium level after process change was non-detectable (< $0.1{\mu}g/m^3$). The number of T lymphocytes and the amount of immunoglobulins in the beryllium-exposed workers and control subjects were not significantly different, except for the total number of lymphocytes and CD95 (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed individuals than in the healthy control subjects. Multiple logistic regression analysis showed lymphocytes to be affected by beryllium exposure (odd ratio = 7.293; p<0.001). These results show that short-term exposure to beryllium does not induce immune dysfunction but is probably associated with lymphocytes proliferation.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.384-393
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• 2017

Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

• IMMUNE NETWORK
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• v.23 no.3
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• pp.25.1-25.15
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• 2023

Mucosal environments harbour lymphocytes, which express several adhesion molecules, including intestinal homing receptors and integrin αE/β7 (CD103). CD103 binds E-cadherin, an integrin receptor expressed in intestinal endothelial cells. Its expression not only enables homing or retention of T lymphocytes at these sites but is also associated with increased T lymphocyte activation. However, it is not yet clear how CD103 expression is related to the clinical staging of breast cancer, which is determined by factors such as the size of the tumor (T), the involvement of nearby lymph nodes (N), and presence of metastasis (M). We examined the prognostic significance of CD103 by FACS in 53 breast cancer patients and 46 healthy controls enrolled, and investigated its expression, which contributes to lymphocyte recruitment in tumor tissue. Patients with breast cancer showed increased frequencies of CD103⁺, CD4⁺CD103⁺, and CD8⁺CD103⁺ cells compared to controls. CD103 was expressed at a high level on the surfaces of tumor-infiltrating lymphocytes in patients with breast cancer. Its expression in peripheral blood was not correlated with clinical TNM stage. To determine the localisation of CD103⁺ cells in breast tissue, tissue sections of breast tumors were stained for CD103. In tissue sections of breast tumors stained for CD103, its expression in T lymphocytes was higher compared to normal breast tissue. In addition, CD103⁺ cells expressed higher levels of receptors for inflammatory chemokines, compared to CD103^- cells. CD103⁺ cells in peripheral blood and tumor tissue might be an important source of tumor-infiltrating lymphocyte trafficking, homing, and retention in cancer patients.

• Journal of Life Science
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• v.21 no.10
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• pp.1401-1406
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• 2011

Morphological changes in immune cells occur due to pathogen infection and natural circulation. T cells produce uropod, filopodia, lamellipodia, and microvilli for inflammation, immunosurvelliance, migration, and diapedesis. Short finger-like microvilli cover the surfaces of circulating mammalian immune cells. The surface features of monocytes and neutrophils are quite different, containing membrane ruffles as their predominant structure. In this study, we present the involvement of actin cytoskeleton regarding T lymphocyte microvilli. From analysis of scanning electron micrographs, Jurkat T lymphocyte microvilli was observed to rapidly disassemble when exposed to the actin-sequestering molecule, cytochalasin D. In contrast to cytochalasin D treatment, we found that median microvillar thickness was enlarged on Jurkat T lymphocytes treated with PMA via Lin-11, Isl-1, Mec-3 Kinase (LIMK) and cofilin signaling. In addition, actin cytoskeleton was involved in polarity formation in EL4 T lymphocytes. These results suggest that microvilli formation or polarity of T lymphocytes are involved in actin cytoskeleton dynamics.

• YAKHAK HOEJI
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• v.35 no.3
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• pp.174-181
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• 1991

These experiments were conducted to investigate the effects of glycyrrhizin(GL) and glycyrrhetinic acid(GA) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [sup 3/H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}$Ca$^{2+}$ to P388D$_{1}$, cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GL(10$^{-3}$M) and GA(10$^{-4}$M). Histamine production in mouse spleen cell culture was significantly increased by the addition of 0.25 $\mu\textrm{g}$/ml of Con A, after 48 hour incubation. Con A dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 .mu.g/ml of Con A. The effects of GL on histamine contents and T-lymphocyte proliferation were significantly decreased at high dose (10$^{-5}$M), while IL-1 activity was remarkably suppressed by 10$^{-8}$~10$^{-4}$M of GL. $Ca^{2+}$ uptake was not changed, but antibody production was increased by GL(10 mg/kg). GA inhibited histamine contents at 10$^{-9}$~10$^{-7}$ and depressed Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-7}$~10$^{-5}$M of GA, but increased suboptimal dose (Con A 0.1 $\mu\textrm{g}$/ml) at 10$^{-9}$~10$^{-7}$M of GA. IL-1 activity was suppressed by 10$^{-8}$~10$^{-4}$M of GA and $Ca^{2+}$ uptake was enhanced by 10$^{-9}$~10$^{-6}$ of GA, but antibody production was not changed by GA. From the above results, it is suggested that GL and GA have immuno-regulatory action. GL decreased cell-mediated immune response, and increased humoral immune response at high dose. On the other hand, low dose of GA enhanced cell-mediated immune response, while high doses of GA decreased humoral immune reaction.

• Journal of Microbiology and Biotechnology
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• v.18 no.3
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• pp.600-610
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• 2008

A cancer-associated antigen gene (CAGE) was identified by serological analysis of a recombinant cDNA expression library (SEREX). The gene was identified by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera from patients with gastric cancer. CAGE was found to contain a D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. The CAGE gene is widely expressed in various cancer tissues and cancer cell lines. Demethylation plays a role in the activation of CAGE in certain cancer cell lines where the gene is not expressed. The functional roles of CAGE in tumorigenesis, the molecular mechanisms of CAGE expression, and cell motility are also discussed.

• Radiation Oncology Journal
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• v.34 no.4
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• pp.250-259
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• 2016

Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

• IMMUNE NETWORK
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• v.9 no.2
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• pp.53-57
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• 2009

Engagement of the immunoreceptors initiates signaling cascades resulting in lymphocyte activation and differentiation to effector cells, which are essential for the elimination of pathogens from the body. For the transduction of these immunoreceptor-mediated signals, several linker proteins termed transmembrane adaptor proteins (TRAPs) were shown to be required. TRAPs serve as platforms for the assembly and membrane targeting of the specific signaling proteins. Among seven TRAPs identified so far, LAT and LIME were shown to act as a positive regulator in TCR-mediated signaling pathways. In this review, we will discuss the functions of LAT and LIME in modulating T cell development, activation and differentiation.

• Korean Journal of Pharmacognosy
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• v.37 no.3
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• pp.212-216
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• 2006

The effect of aqueous extracts of medicinal plants $AMP-365^{TM}$ was tested for immune system regulating activity based on anti-inflammatory activity, anti-oxidant, macrophage proliferation and T-lymphocyte proliferation activity. $AMP-365^{TM}$ dose-dependently increased proliferation of RAW264.7 macrophage cells and its nitric oxide production as well as DPPH radical scavenging activity. On the other hand, T-lymphocyte proliferation activity was decreased on dose-dependent manner. Passive cutaneous anaphylaxis reaction was alleviated by 49% by administering 250 mg/kg of $AMP-365^{TM}$. The results suggest that $AMP-365^{TM}$ can be beneficial in the treatment of immediate allergic reactions as an adjuvant supplement material.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.267-270
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• 1995

We examined the chronic effect of dextromethorphan(DM) on the cellular immune responses in mice. T cell simulator, phytohemagglutinin did not show singificant effect on lymphocyte proliferation. Costimulator of T and B cell, pokeweed mitogen, and B cell stimulator, lipopolysaccharide exhibited DM-induced decreased lymphocyte proliferation. Singificantly suppressed natural killer (NR) cell cytotoxicity was evidenced following 6 months DM exposure. These results suggest that chronic DM administration pertub B cell functioning and NK cell cytotoxicity. In addition, prenatal DM exposure did not potentiate the immunomodulation in postnatal effect induced by chronic DM.