• Toxicological Research
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• 제29권2호
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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.

• 한국임상수의학회지
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• 제8권1호
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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.

• 대한의생명과학회지
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• 제20권3호
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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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• 제17권4호
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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.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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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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• 제22권1호
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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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• 제14권1호
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• pp.53-59
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• 1996

목적 : 암환자에서 방사선치료에 의한 면역기능의 저하에 대해서는 많은 보고가 되어 있다. 저자들은 방사선치료부위중 비교적 활동성 골수를 많이 포함하고 있는 흥부 및 골반강조사 직후 어느정도 면역력의 저하가 오는지 알아보고자 하였다. 대상 및 방법 : 1995년 1월부터 1995년 4월까지 등록된 61 명의 환자중 48 명을 대상으로 분석 하였다. 이중 흉부(조사문, >$150cm^2$)에 방사선치료를 시행한 환자는 29명이었고 전골반강부에 방사선치료를 시행한 환자는 19명 이었다. 연령분포는 36세에서 73세 였으며 평균 및 중간값 모두 57세 였으며 남녀비는 1.3(27/21)이었다. 환자의 면역기능의 지표는 말초혈액검사에서 전혈구 및 감별혈구계산(CBC with D/C), 간기능검사, 신장기능검사 및 림프구아형검사(CD3, CD4, CD8, CDl6, CD56, CDl9)를 시행 하였으며, 검사시기는 방사선치료 직전과 4500 cGy - 5000 cGy 선량에서 동일 검사를 반복시행 하였으며, 1980cGy에서는 전혈구 및 감별혈구계산만 시행하였다. 결과 : 전체환자의 치료전 백혈구 총수는 7017이었으며 방사선치료직후 평균 4470으로 감소하였다(p=0.0000). 감별혈구계산에서는, 림프구수는 평균 2047 에서 537 로(p=0.0000) 로 감소하였고, 호중구, 호염구세포의 절대수도 통계학적으로 유의한 감소를 보였으나, 단핵세포는 변화가 없었으며, 호산구세포는 오히려 방사선치료후 증가하였으나 통계적인 의의는 없었다. 림프구아형에 대한 검사결과는, 모든아형의 절대수가 통계학적으로 유의한 감소를 보였으며, CD4/CD8비는 치료전 평균 1.09에서 0.99로 감소 하였으나 통계적인 유의성은 없었다. 전체 림프구에 대한 비율의 변화를 보면, B림프구(CD 19)는 감소하였으나, 그외 아형의 비율은 방사선치료후 변화를 보이지 않았다. 혈청면역글로불린은 초기 Ig, G, Ig A, Ig M 모두 정상값보다 눌은 수치였으며, 방사선치료에 따른 변화는 Ig M에서만이 통계적으로 유의한 감소를 보였으며, Ig G, A는유의한 변화가 없었다. 결론 : 흉부나 골반강부위의 방사선치료는 림프구의 급격한 저하를 초래하는 반면 단핵구등은 비교적 잘 유지 되었으며, 호산구는 오히려 증가 됨을 알수 있었으나, 인체의 면역과의 관계를 설명하기 위해서는 림프구의 기능변화가 함께 연구 되어져야 하겠다.

• Journal of Nutrition and Health
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• 제27권2호
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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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• 제43권11호
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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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• 제13권1_2호
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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.