• 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 Veterinary Clinics
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• v.8 no.1
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• pp.1-10
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• 1991

The B-lymphocyte differentiation from committed B-cell progenitors to antibody-secreting cells was discussed. B-cell progenitors derived from hematopoietic stem cells undergo the rearrangement of immunoglobulin(Ig) gene. The earliest cells as B-cell precursors have cytoplasmic Is(${\mu}$ chain). The entire Is molecule is expressed on the surface after synthesis of L chain. The resting B cells(Go stage) stimulated by binding antigen via Ig-receptors are activated(G$_1$ stage) and followed by proliferation(S stage), coupled with further selection(affinity maturation. class switch). The production of antibody against a particular antigen depends on the activation of B cells with surface Is capable of reacting with that antigen. This process does not occur in isolation but is controlled by helper and suppressor T cells and antigen presenting cells(APC). The mechanism of T cell-dependent B-cell response for production of antibody is largely explained by the cell to cell cooperation and soluble helper factors of T cells. 1) The antigen specific B cells and helper T cells are linked by Is-receptors, leading to the delivery of helper signals to the B cells. 2) Helper T cells recognize the processed antigen-derived peptides with the MHC class II molecules(la antigen) and is stimulated to secrete B-cell proliferation and differentiation factors which activate B cells of different antigenic specificity. The two models are shown currently 1) At low antigen concentration, only the antigen-specific B cell binds antigen and presents antigen-derived peptides with la molecules to helper T cells, which are stimulated to secrete cytokines(IL-4, IL-5, etc.) and 2) At high antigen concentration, antigen-derived peptides are presented by specific B cells, by B cells that endocytose the antigens, as well as by APC Cytokines secreted from helper T cells also lead to the activation of B cells and even bystander B cells in the on- vironmment and differentiate them into antibody-secreting plasma cells.

• Biomedical Science Letters
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• v.20 no.3
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• pp.147-155
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• 2014

It has well studied that immune cells are strongly related to tumor progression and tumor suppression. To identify the difference of immune cell between tumor bearing mice and normal mice, we examined systemically the immune cell of CT26 tumor bearing mice on 21 days after tumor cell administration. As previously reported, CD4+ and CD8+ T cells population of tumor bearing mice significantly decreased 38% and 30% on day 21 compared to that of normal mice, respectively. All subpopulation of CD4 and CD8+ T cell significantly decreased, except CD49b+ T cell subpopulation. But, myeloid cell population ($CD11b^{high}$ and all Gr-1+ subpopulation) of tumor bearing mice significantly increased on day 21. Especially, all subpopulation of CD11b+Gr-1+ cell of tumor bearing mice significantly increased on day 21. Also, Foxp3+$CD25^{high}$ CD4 T cell (regulatory T cells) population significantly increased on day 21. These results suggest that tumor can induce the decline of T lymphocyte and the expansion of myeloid cells and regulatory T cells, and provide the basic information for the study of tumor immunology.

• 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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.175-175
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• 2003

In the present study, we show the inhibitory effect of anethole, a substituted alkenylbenzene found in a variety of foods and essential oils, on T lymphocyte functions. Anethole produced an inhibition of concanavalin A-induced lymphoproliferation in B6C3F1 mouse splenocytes.(omitted)

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.1
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• pp.20-25
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• 2009

Xenotransplantation of pig organs into humans is a potential solution for the shortage of donor organs for transplantation. However, multiple immune barriers preclude its clinical application. In particular, the initial type of rejection in xenotransplantation is an acute cellular rejection by host $CD8^+$ cytotoxic T lymphocyte (CTL) cells that react to donor major histocompatibility complex (MHC) class I. The human cytomegalovirus (HCMV) glycoprotein Unique Short (US) 2 specifically targets MHC class I heavy chains to relocate them from the endoplasmic reticulum (ER) membrane to the cytosol, where they are degraded by the proteasome. In this study we transfected the US2 gene into minipig fetal fibroblasts and established four US2 clonal cell lines. The integration of US2 into transgenic fetal cells was confirmed using PCR and Southern blot assay. The reduction of Swine Leukocyte Antigen (SLA)-I by US2 was also detected using Flow cytometry assay (FACS). The FACS analysis of the US2 clonal cell lines demonstrated a substantial reduction in SLA-I surface expression. The level (44% to 76%) of SLA-I expression in US2 clonal cell lines was decreased relative to the control. In cytotoxicity assay the rate of $CD8^+$ T cell-mediated cytotoxicity was significantly reduced to 23.8${\pm}$15.1% compared to the control (59.8${\pm}$8.4%, p<0.05). In conclusion, US2 can directly protect against $CD8^+$-mediated cell lysis. These results indicate that the expression of US2 in pig cells may provide a new approach to overcome the CTL-mediated immune rejection in xenotransplantation.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.53-59
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• 1996

Purpose : Radiation-induced alteration in the immune function is well known phenomenon in cancer patients. Our purpose is to evaluate the extent of immune suppression immediately after mediastinal or pelvic irradiation, which include significant volume of active bone marrow in adults. Materials and Methods'48 cancer patients with mediastinal(N=29) and pelvic irradiation(N=19) were the basis of this analysis. Age ranged from 36 to 76 and mean and median value was 57 years, respectively Sex ratio was 1.3(M: F=27/21). The immunological parameters were the complete blood cell(CBC) with differential cell(D/C) count, T cell subset(CD3, CD4, CD8 CDl9), NK cell test(CDl6, CD56), and serum immunoglobulin(IgG, IgA, IgM) level. Results : The mean value of white blood cell(WBC) was reduced from 7017 to 4470 after irradiation(p=0.0000). In the differential count, the number of lymphocyte, neutrophil, and basophil was markedly reduced with statistical significance(p<0.01) and the number of monocyte was not changed and, on the contrary, that of eosinophil was increased by irradiation. In the lymphocyte subpopulation analysis, the number of all subpopulations, CD3(T cell), CD4(helper T cell), CD8(suppressor T cell), CDl6(NK cell), CDl9(B, cell) was reduced with statistical significance. The mean ratio of CD4 to CD8 in all patients was 1.09 initially and reduced to 0.99 after radiotherapy(p=0.34) , but the proportional percentage of all subpopulations was not changed except CD19(B cell) after irradiation. In the immunoglobulin study, initial values of Ig G, Ig A, and Ig M were relatively above the normal range and the only Ig M was statistically significantly reduced after radiotherapy(p=0.02). Conclusion : Mediastinal and pelvic irradiation resulted in remarkable suppression of lymphocyte count in contrast to the relatively good preservation of other components of white blood cells. But the further study on the functional changes of lymphocyte after radiotherapy may be necessary to conclude the effects of the radiation on the immunity of the cancer Patients.

• Journal of Nutrition and Health
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• v.27 no.2
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• pp.153-161
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• 1994

We fed high trypotophan diet(3.5% tryptophan/diet(w/w) to mice for 7 days and treated then with 3 hour immobilization(IMMB) stress to investigate tryptophan metabolism and immunomodulation. The levels of serum tryptophan, brain tryptophan, serotonin(5HT) and 5-hydroxyindoleacetic acid(5HIAA) in the tryptophan diet fed animals were higher than those of the normal diet fed animals. Feeding tryptophan supplemented diet to stressed animal significantly decreased the levels of serum and brain tryptophan and 5HT levels. However, the amount of 5HIAA which is the metabolite of serotonin was increased in brain. Plasma corticosterone level was increased by the stress in both groups but the degree of this increase was smaller in high tryptophan fed animals. The relative numbers of CD8+ T cells, CD4+ T cells and B cells in spleen were decreased in high tryptophan diet fed and stressed animals compared to control diet fed and no stressed animals. CD8+ T cells decreased more than CD4+ T cells. The decrease of CD8+ T cells in high tryptophan fed and stressed animals was similar to that in high tryptophan fed animals or normal diet fed and stressed animals. Stress and tryptophan supplement acted synergistically to decrease the number of B cells. This study suggests that stress and tryptophan supplement could modify the number of lymphocyte cells, and indicates that the interaction of stress and tryptophan supplement on immune fuction depends on the types of immune cells.

• Molecules and Cells
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• v.43 no.11
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• pp.921-934
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• 2020

Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME^-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME^-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME^-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.

• Environmental Analysis Health and Toxicology
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• v.13 no.1_2
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• pp.33-41
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• 1998

Chlorpyrifos, o,o diethyl-o-(3,5,6-trichloro-2-pyridyl) phosphorothioate, is a broad spectrum organophosphate insecticide. The use of chlorpyrifos has been increased more and more as pesticide. But the effects of chlorpyrifos on the immune alterations has not been yet observed. Therefore, we investigated the effects of chlorpyrifos on the immune alterations in CICA male mice. Chlorpyrifos was administered to mice by a single intraperitoneal injection for the purpose of observing acute effects. On the one hand to get the information on immunopathologic alterations we observed hematological values, counted total circulating leukocytes and assessed the ratio of lymphocytes and neutrophils from the peripheral blood, measured the ratio of organ/body weight and counted splenic cellularity in CBA male mice which treated chlorpyrifos intraperitoneally. But we could not find any significant immunopathologic alterations statistically by a single intraperitoneal injection. Also, the exposure of chlorpyrifos caused no significant change in the number of PFC/10$^6$ spleen cells at any three given doses. On the other hand a singte intraperitoneal injection of chlorpyrifos decreased the lymphocyte proliferation response slightly to ConA or LPS stimulation at a dose of 6 mg/kg b.w. Administrations of chlorpyrifos reduced mixed leukocyte response(MLR). MLR was decreased moderately at doses of 3mg/kg b.w. and 6mg/kg b.w. Therefore, all these findings suggest that chlorpyrifos may alter the immune functions acutely. especially by the changes of T lymphocyte activity.