• Journal of Microbiology and Biotechnology
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• 제22권8호
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• pp.1066-1076
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• 2012

Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.

• Molecules and Cells
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• 제45권8호
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• pp.513-521
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• 2022

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule that is mainly expressed on activated T cells and regulatory T (Treg) cells that inhibits T-cell activation and regulates immune homeostasis. Due to the crucial functions of CTLA-4 in T-cell biology, CTLA-4-targeted immunotherapies have been developed for autoimmune disease as well as cancers. CTLA-4 is known to compete with CD28 to interact with B7, but some studies have revealed that its downstream signaling is independent of its ligand interaction. As a signaling domain of CTLA-4, the tyrosine motif plays a role in inhibiting T-cell activation. Recently, the lysine motif has been shown to be required for the function of Treg cells, emphasizing the importance of CTLA-4 signaling. In this review, we summarize the current understanding of CTLA-4 biology and molecular signaling events and discuss strategies to target CTLA-4 signaling for immune modulation and disease therapy.

• 대한수의학회지
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• 제50권3호
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• pp.179-185
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• 2010

The present study was undertaken to establish reference values for the composition blood lymphocyte populations and compare forty three Hanwoo neonatal calves (KC) with twenty one Holstein calves (HC) by blood cell count and immunophynotying. The percentages of CD2+, CD4+, CD8+, CD26+, ACT2+, MHC class, MHC class II and WC1+ T cells, B cells were determined by flow cytometry. The number of lymphocyte and monocyte in HC were higher than those of KC. However, the number of neutrophils was higher in HC than KC. The proportions of CD2+, CD4+, CD8+, MHC class, and WC1+ lymphocytes remained relatively stable during the study period, while there was a moderate increase in the relative percentage of CD26+, ACT2+, MHC class II and B cell from birth to approximately 3 weeks of age. Marked differences in the relative proportions of the lymphocyte subpopulations were noted between the individual calves. The present study shows that the T-cell subpopulations are present in peripheral blood of KC at levels comparable with HC, while the MHC class II and B cell population of KC increases significantly with age. The absolute number of WBC in KC was due to the decrease of absolute number of neutrophil rather than the increase of lymphocyte. The results indicated that KC have significantly higher number of neutrophils, and proportion of MHC class II and B cell than HC.

• Journal of Periodontal and Implant Science
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• 제23권2호
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• pp.300-314
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• 1993

Periodontal disease research has been focused on understanding the immunopathologic mechanisms which may operate in the development and maintenance of peiodontal inflammatory changes. Immunologic and inflammatory responses may relate to the etiology and pathogenesis of periodontal disease. In order to research immunopathology of periodontal disease, previous investigators have spent much time on the distribution of lymphocyte subpopulations and NK cells but they have spent less time on the changes of those cells to the periodontal disease severity. The purpose of study was performed to investigate the changes of the distribution of T lymphocytes, B lymphocytes, T lymphocyte subsets, and Natural Killer cells in the gingival epithelium and connective tissue of the periodontal disease with the various clinical parameters including Gingival Index, Sulcular Bleeding Index, and pocket depth. Gingival tissues were obtained from 25 patients with different severity of periodontal disease. Serial cryostat sections displaying a cross section of gingiva were labelled with monoclonal antibody for pan T cells, T cytotoxic/suppressor cells, T helper/inducer cells, pan B cells, and NK cells were develped using an avidin-biotin-peroxidase system. Lymphocyte populations were enumerated in repeatable fields from gingival section. 1. T cells were more increased at grade 1 and 3 than at grade 0 of gingival index (p<0.05). Helper T cells and NK cells were significantly increased at grade 1, 2, 3 than at grade 0(p<0.05). 2. T cells were more decreased at grade 3 and 4 than at grade 1 of sulcular bleeding index (p<0.01, p<0.05). Especially, Natural Killer cells were significantly increased at grade 1, 2, 3, 4 than at grade 0 (p<0.05, p<0.001). 3. The ratios of helper T/suppressor T cells were more decreased at grade 4 than at grade 0 and at grade 4 than at grade 2 of sulcular bleeding index (p<0.05, p<0.05). 4. Helper T cells were significantly decreased at grade II and III than at grade I, however the Natural Killer cells showed a increasing tendency with the increase of the pocket depth, there were no significant differences between each grade of pocket depth. 5. The ratios of helper T/suppressor T cells were tended to be decreased with the increase of the pocket depth, there were no significant differences between each grades of pocket depth. There was a very weak change in the distribution of T lymphocytes, B lymphocytes, T lymphocyte subsets, and Natural Killer cells in the gingival epithelium and connective tissue of the periodontal lesion with the various clinical parameters including gingial index, sulcular bleeding index, and pocket depth. But, the number of T lymphocytes and Natural Killer cells were significantly changed in gingival index and sulcular bleeding index.

• 대한예방한의학회지
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• 제5권1호
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• pp.103-115
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• 2001

Background : Gamisamryungbaekchul-san(加味蔘?白朮散) is a herbal medicine which has been used for the traditional therapeutic agent of augmentation of the spleen and reinforcement of the Qi. Objective : This Study was performed to investigate the effect of Gamisamryungbaekchul-san on the tumor and immune response in the moose B16 melanoma tumor model. Materials and Methods : The tumor was induced by subcutaneous inoculation of B16BL6 melanoma cells in the shaved dorsal region of mice. Mice were orally administered with Gamisamryungbaekchul-san extract(26.3mg/mouse) for 14days after inoculation. For making examination of antitumor effect, the Increase of life span, Tumor growth inhibition rate, change of body weight were measured and evaluated. For the immune response increasing effect, the percentage of T lymphocyte and B Lymphocyte in the peripheral blood, the percentage of CD4+ T-cell, CD8+ T-cell and CD4+/CD8+ ratio in the peripheral blood and spleen, interleukin-2 productivity were measured and evaluated. Results : Gamisamryungbaekchul-san showed 16.59% increase of life span, 31.64% tumor growth inhibition rate and increase of body weight. Gamisamryungbaekchul-san increased the percentage of T lymphocyte in the peripheral blood, CD4+ T cell percentage of peripheral blood and spleen, and Interleukin-2 productivity as compared with the Control group. Whereas Gamisamryungbaekchul-san had no effect on the percentage of B lymphocyte in the peripheral blood, the percentage of CD8+ T cell, CD4+/CD8+ T-cell ratio in both of peripheral blood and spleen as compared with the Control group. Conclusion : This study shows that Gamisamryungbaekchul-san has anti-tumor effects and immunoregulatory effects on the B16 melanoma tumor model. It is suggested that Gamisarmyungbaekchul-san could be a useful immunomodulator and anti-tumor agent.

• Restorative Dentistry and Endodontics
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• 제20권1호
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• pp.235-249
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• 1995

This study was designed to identify the lymphocytes present and to examine the relation between lymphocytes population and clinical symptoms of the pulps clinically diagnosed as normal and irreversible pulpitis. We recorded the history and severity of the pain and performed several clinical tests, before extirpation of vital, irreversibly inflamed pulps in routine endodontic treatment. Then the teeth were divided into two groups. Five teeth, categorized in acute symptom group, had severe spontaneous pain, particularly at night and were extremely sensitive to cold and heat. The other 15 teeth with history of mild to moderate pain and with or without cold or heat responses were categorized as chronic symptom group. Inflamed pulps were also classified into 8 minor groups by presence or absence of signs or symptoms related to the involved teeth, including the presence of pain on percussion, pain on heat and cold stimuli and the periodontal pocket depth. All extirpated pulps were immediately immersed in ultra low-temperature freezer($-74^{\circ}C$), and they were sectioned $6{\mu}m$ in thickness. Specimens were stained using three-stage indirect immunoperoxidase techniques(DAKO, LSAB kit) and monoclonal antibodies for detecting the presence of T lymphocytes(T), B lymphocytes(B) and helper(T4) and suppressor(T8) lymphocytes. Following results were obtained; 1. All the examined normal and inflamed pull) tissues had positive staining for T lymphocytes and T helper and T suppressor cells. But B cells were observed only in inflamed pulp. 2. Statistically more T and B cells were observed in acute symptom group as compared with chronic symptom group(p<0.05). 3. Cell ratio of BIT in acute symptom group were significantly higher than that of chronic symptom group(p<0.05). 4. Only B cells were significantly increased in the percussion positive group than the number of B cells in percussion negative group(p<0.05). 5. No differences were observed in the number of different cell types among other minor groups.

• 생명과학회지
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• 제20권2호
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• pp.304-313
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• 2010

J시 소재 K여자고등학교 1학년 중에서 %fat이 30% 이상인 24명을 유의추출법에 의해 운동그룹 A (8명), B (8명) 그룹과 통제그룹(8명)으로 3그룹으로 구분하여 Borg의 주관적운동강도를 이용, A그룹은 RPE 15-17 (hard-very hard; 힘듦-매우 힘듦)${\times}$3 sets, B그룹은 RPE 11-13 (fairly light-somewhat hard; 알맞음-약간 힘듦)${\times}$3 sets로 설정하여 step aerobics (step box: 길이 68 cm, 폭 28 cm, 높이 15 cm, 무게 450 g)를 1일 50-60분간, 주3회(월, 수, 금)로 총 8주간 실시하였다. 본 연구는 step aerobics의 RPE가 비만 여고생의 면역기능(Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil, IgG, IgA, IgM)에 어떠한 영향을 미치는가를 알아보는 것이었다. 자료처리는 SPSS Ver. 14.0을 이용하여 집단과 시기 간 상호작용의 효과를 알아보기 위하여 repeated two-way ANOVA를, 집단 내 운동 전 후는 paired t-test를 실시하였고, 집단 간은 변화율(% diff.)을 구하여 one-way ANOVA를 실시하여 다음과 같은 결론을 얻었다. WBC에서, 집단 내 비교에서 A그룹은 Neutrophil, Monocyte, Basophil, Eosinophil 모두 증가하였으나 Lymphocyte는 변화가 없었고, B그룹은 Eosinophil은 감소하였으나 Neutrophil, Lymphocyte, Monocyte, Basophil 모두 변화가 없었으며, 통제군은 Neutrophil, Basophil, Eosinophil은 감소하였으나 Lymphocyte와 Monocyte는 변화가 없었다. 집단 간 비교의 Neutrophil은 A그룹이 B그룹과 통제군보다 더 많이 증가하였고, Lymphocyte는 집단 간 차이가 없었으며, Monocyte는 A, B그룹이 통제군보다 많이 증가하였다. Basophil과 Eosinophil은 A그룹이 B그룹과 통제군보다 더 많이 증가하였다. Immunoglobin에서, 집단 내 비교에서 A그룹은 IgG는 증가하였으나 IgA와 IgM는 변화가 없었고, A그룹은 IgA는 증가하였으나 IgG는 감소하였고 IgM은 변화가 없었다. 통제군은 IgG은 감소하였으나 IgA와 IgM은 변화가 없었다. 집단 간 비교의 IgA는 A그룹이 통제군보다 증가하였고, IgG는 A그룹이 B그룹과 통제군보다 증가하였으나 IgM은 집단 간 차이가 없었다. 요약하면 세 집단 모두 운동프로그램 전 후의 WBC와 Ig 수준이 연령에 맞게 참고치 내의 수준에 머물렀지만 step aerobics를 RPE 15-17로 실시한 A그룹의 경우가 가장 많은 측정항목에서 증가를 보였고, 이 결과는 참고치 범위 내에서 면역기능의 항진을 보여주는 것으로 면역기능의 향상을 위한 step aerobics의 RPE 강도는 힘듦-매우 힘듦(15-17)의 수준으로 실시하는 것이 효과적인 것으로 생각된다.

• 대한한의학회지
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• 제20권1호
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• pp.75-83
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• 1999

To investigate the effects of negative therapy at back meridian points on blood gas components and immune functions in male college students, this study was conducted on treatment types(abdomen group and back group) at three sampling times (before, post-2 wks and post-4 wks) by using $2{\times}3$ factoral design. Blood gas $components(pH,\;PCO_2,\;PO_2,\;HCO_3^-,\;O_2SAT,\;BE)$, red blood cell, hematocrit, hemoglobin, white blood cell and subsets(neutrophil, basophil, eosinophil. lymphocyte, monocyte), total T cells, helper T cells, suppressor T cells, Th/Ts ratio, total B cells, serum immunoglobulin levels (IgG, IgA, IgM, IgD, IgE), Cytokines(Interlukin$-1{\beta}$, -2, -4, 2 receptor, -6 and ${\gamma}$-interferon), NK cells were measured. Collected with data were analyzed statistically by repealed measured ANOVA. The pattern of change between two groups for hematocrit, hemoglobin, suppressor T cells, interleukin-6, ${\gamma}-interferon$, NK cells at post-2 weeks and BE, lymphocyte, basophil at post-4 weeks was significantly different(p<0.05) And also the pattern of change over time for ${HCO_3}^-$(2 wks vs 4 wks), WBC, neutrophil, lymphocyte(0 wks vs 2 wks and 2 wks vs 4 wks) was significantly different(p<0.05). In summary, these data suggest that negative therapy at back meridian points had an effect on blood gas components and immune functions in male college students because practicing negative therapy at back meridian points was not associated with changes of all blood gas components and immune factors but associated with changes of BE, hematocrit, hemoglobin, WBC. neutrophil, lymphocyte, interleukin-6. ${\gamma}-interferon$, NK cells.

• Preventive Nutrition and Food Science
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• 제15권1호
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• pp.19-23
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• 2010

This study examined the effects of Acrylamide (ACR) and L-ascorbic acid (AsA) on the proliferation of splenocytes and the mitogen-stimulated lymphocyte proliferation in young (8 weeks) and aged (82 weeks) C57BL/6male mice in vitro. AsA increased splenocyte proliferation in both groups; however, this effect was higher in old mice, while the proliferation of lymphocyte was decreased except for treatment at $1\;{\mu}g/mL$ low concentration in both mice. In addition, ACR treatment resulted in decreased LPS-induced B lymphocyte proliferation and ConA-induced T lymphocyte proliferation in both groups. However, AsA increased LPS/ConA-induced lymphocyte proliferation in young groups and had no effects in old mice except at $0.5\;{\mu}g/mL$ Thus, the present data indicate that there is no difference effect of ACR and AsA on lymphocyte proliferation, whereas the effect of AsA on mitogen-induced cell proliferation was reduced in old mice. Overall, our results suggest that various immunomodulators have differing effects of lymphocytic proliferation on young versus aged mice.

• Archives of Pharmacal Research
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• 제18권4호
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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.