• Title/Summary/Keyword: T-lymphocytes

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Effects of Vitamin E Derivative TMG on the Radiation Protector and Tumor Growth during Radiotherapy

  • Yeun-Hwa Gu;Ryo Matsumoto;Takenori Yamashita
    • Journal of Radiation Protection and Research
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    • v.48 no.1
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    • pp.1-8
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    • 2023
  • Background: The purpose of this study is to evaluate the immunosuppressive and antioxidant effects of a novel radioprotective agent using the vitamin E derivative 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG) and its effect on tumors, and to study its usefulness. Materials and Methods: In this study, C57BL/6NCrSlc mice were divided into four groups (control, TMG, radiation therapy [RT], and RT+TMG), using 10 mice in each group. In the TMG and 2 Gy+TMG groups, 500 mg/kg TMG was administered. Two groups (2 Gy and 2 Gy+TMG) among RT and RT+TMG groups were irradiated with 2 Gy in a single fraction, while the other two groups (6 Gy and 6 Gy+TMG) were irradiated locally with 6 Gy in three fractions. Results and Discussion: TMG positively affected CD4+ and CD8+ T lymphocytes. Tumor volumes and growth inhibition rates were compared. In order to evaluate how TMG administration affected tumor growth, Ehrlich cancer cells were injected into the thigh of mice, and the tumor volume and growth suppression rate were compared. Not only RT but also TMG alone inhibited tumor growth. If RT conducted to the mice with TMG, TMG could increase the number of leukocytes, primarily that of lymphocytes. TMG also inhibited tumor growth in addition to RT. Tumor growth was significantly inhibited in the 6 Gy+TMG group. Conclusion: In conclusion, TMG exerted an immunopotentiating effect mainly by increasing the white blood cell numbers including that of lymphocytes. In addition to RT, TMG also inhibited tumor growth. Therefore, TMG is considered to be a useful radioprotective agent in radiotherapy without tumor growth induction.

Induction of CEA-specific Cytotoxic T Lymphocytes by Murine Dendritic Cells Expressing CEA (CEA 발현 수지상 세포를 이용한 CEA 특이 살해 T 세포의 유도)

  • Won, Eun-Ha;Kim, Chang-Hyun;Park, Mi-Young;Cho, Hyun-Il;Oh, Seong-Taek;Hong, Yong-Kil;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.3 no.4
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    • pp.295-301
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    • 2003
  • Background: Carcinoembryonic antigen (CEA) is well-known soluble tumor marker frequently detectable in peripheral blood of carcinoma patients and considered as good target for antigen-specific immunotherapy. In this study, we used a replication-deficient adenovirus containing CEA to study CTL induction in vitro after adenovirus-mediated gene transfer into DC. Methods: DC were obtained from mouse bone marrow and cultured with IL-4 and GM-CSF. For measuring CTL activity, splenocytes were harvested from the mice, which were immunized with DC that had been infected AdV-CEA or pulsed with CEA peptide. Untreated DC was used as a control. Splenocytes were re-stimulated in vitro with DC pulsed with CEA peptide for 7 days and CTL activity with CEA peptide-pulsed EL-4 cells were assessed in a standard $^{51}Cr$-release assay. The frequencies of antigen-specific cytokine-secreting T cell were determined with $mIFN-{\gamma}$ELISPOT. Results: DC infected with recombinant adenovirus expressing CEA induced CEA-specific CTL responses in vivo. Splenocyte induced from mice immunized with AdV-CEA-infected DC increase in the number of $IFN-{\gamma}$ secreting T cells compared with those from mice immunized with CEA peptide-pulsed DC. Conclusion: These results suggested that DC infected with recombinant adenovirus has advantages over other forms of vaccination and could provide an alternative approach vaccination therapies.

Increased Frequency of Foxp3+ Regulatory T Cells in Mice with Hepatocellular Carcinoma

  • Du, Yong;Chen, Xin;Huang, Zhi-Ming;Ye, Xiao-Hua;Niu, Qing
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3815-3819
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    • 2012
  • The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

Role of Rho A and F-actin for uropod formation in T lymphocytes (T 세포의 Uropod 형성에 있어 Rho A와 F-actin의 역할)

  • Lee, Jong-Hwan
    • Journal of Life Science
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    • v.17 no.2 s.82
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    • pp.192-197
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    • 2007
  • Two distinct morphological features, leading edge and uropod, in mobile T lymphocyte are crucial for efficient directional movement. The uropod is a unique rear protrusion in migrating lymphocytes, in which several proteins, including CD44, ERM (ezrin/radixin/moesin), and F-actin cytoskeleton are concentrated and concerted. F-actin cytoskeleton is a basic mold for the shape maintenance. Rho A small GTPase acts as cytoskeleton organizer, So far, various pathways potentially can induce the Rho activation. PDZ domain is able to increase active Rho A form (Rho-GTP) level, reorganize F-actin cytoskeleton, disrupts the uropod structure and cell migration was diminished, suggesting that signaling pathways between Rho and F-artin cytoskeleton are related to uropod formation.

Protective effect of Lycium barbarum leaf extracts on atopic dermatitis: in vitro and in vivo studies

  • Han Sol Lee;Eun Young Bae;Sun Yung Ly
    • Nutrition Research and Practice
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    • v.17 no.5
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    • pp.855-869
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    • 2023
  • BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 ㎍/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.

Partial Purification and Characterization of a Glycoprotein Factor from Fresh Ginseng (수삼으로부터 당단백질 인자의 부분정제와 특성연구)

  • Kong, Yun-Cheung;Fong, Wing-Ping;Song, Myung-Eun;Ng, Kam-Hung;Ho, Dan-Dan;Ng, Ping-Chung
    • Journal of Ginseng Research
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    • v.14 no.2
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    • pp.221-227
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    • 1990
  • The aqueous extract of fresh ginseng (Panax ginseng C.A. Meyer) contains a macromolecular fraction that showed mitogenic and co-mitogenic activities in human peripheral blood lymphocytes. Purification of the crude extract by size (ultrafiltration, Sephadex G-200) and charge (DEAE-cellulose, DEAE-Sepharose) yielded a semi.purified fraction (DS-3). This fraction contains at least three subgroups of anionic macromolecules with apparent molecular weight greater than 600 kilodaltons. It is a glycoprotein with a large amount of glucuronic acid. It acts as a mitogen in both T and B cells of human peripheral blood lymphocytes. It could also potentiate the mitogenic action of Concanavalin A in lymphocyte T cells. Such potentiation is not due to increased binding of Concanavalin A to the cell surface. Its mitogenic and co-mitogenic effects do depend on the presence of extracellular Ca2+.

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Immunomodulatory Effects of Eckol, a Pure Compound of Ecklonia Cava, on Dendritic Cells

  • Kim, Mi-Hyoung;Joo, Hong-Gu
    • IMMUNE NETWORK
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    • v.6 no.4
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    • pp.199-203
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    • 2006
  • Background: Eckol purified from Ecklonia cava, a brown alga has been known to have cytoprotective effects on some cell lines against oxidants and ionizing radiation. However, there is no study about the effects of eckol on immune cells. Methods: Bone marrow (BM)-derived dendritic cells (DCs) were used to demonstrate the immunomodulatory effects of eckol on DCs, such as viability, the expression of surface markers, allogeneic stimulating capacity using MTI, flow cytometric, $^3H$-thymidine incorporation assay. Results: Eckol did protect DCs against cytokine withdrawal-induced apoptosis in a concentration dependent manner based on MTT assay. And also, it increased the expression of MHC class II and CD86 (B7.2) molecules, maturation markers, on the surface of viable DCs gated in FACS analysis. Furthermore, eckol-treated DCs stimulated the proliferation of allogeneic $CD4^+$ T lymphocytes compared to imDCs in $^3H$-thymidine incorporation assay. $CD4^+$ T lymphocytes activated with eckol-treated DCs produced the larger amount of IFN-${\gamma}$ and IL-4 than those cells with imDCs. Conclusion: Taken together, we demonstrate in this study that eckol, a pure compound of Ecklonia cava, may modulate the immune responses through the phenotypic and functional changes of DCs.

Experimental Studies on Activity of the Cultivated Mycelia of Phellinus linteus (상황(桑黃) 배양균사체의 활성에 관한 연구(I))

  • Kong, Young-Yun;Lee, Kwan-Ki;Nam, Sang-Yun;Hong, Nam-Doo
    • Korean Journal of Pharmacognosy
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    • v.22 no.4
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    • pp.233-239
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    • 1991
  • Phellinus linteus was examined for its anticancer activity using an animal model. Water extract of Phellinus linteus was prepared from artificially cultivated mycelia. Neither toxicity nor abnormal changes of hematological parameters were observed in the rat given orally with high doses of drug extract for 15 days. ICR mice were transplanted with Sarcoma-180 tumor cells intraperitoneally and drug extract was daily given to the mice from 1 day after tumer transplantation for 3 weeks. Administration of drug extract significantly prolonged the survival duration of Sarcoma 180-transplanted mice. For the better understanding of the anticancer activity, we have examined the effect of the drug extract administration on various killer cell functions, such as natural killer(NK) cells, cytotoxic T-lymphocytes (CTL) and macrophages which have been known to be main effector cells in immune responses against tumors. The results from the 4 hr $^{51}Cr-release$ assay have shown that the drug extract augments mouse NK cell activity but neither CTL nor macrophages. It is possible, then, that the anticancer activity of the Phellinus linteus may be associated with augmentation of NK cell function in the cancerated hosts.

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Immunosuppressive Characteristics of Oligomycin Derivatives Produced by Streptomyces lydicus MCY-524

  • Lee, Sang-Yong;Han, Sang-Bae;Kim, Hang-Sub;Kim, Young-Ho;Kim, Hwan-Mook;Kim, Chang-Jin;Hong, Soon-Duck;Lee, Jung-Joon
    • Journal of Microbiology and Biotechnology
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    • v.7 no.1
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    • pp.56-61
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    • 1997
  • A strain producing immunosuppressive substances was isolated from a soil in Cheju island. By morphological, cultural, and physiological studies, the strain was identified as Streptomyces lydicus MCY-524. Cultured broth was purified by silica gel, sephadex LH-20 and preparative HPLC and gave two immunosuppressive compounds, MCH-22 and MCH-32. They dramatically suppressed the B cell activation with lipopolysaccharide, T cell activation by mixed lymphocyte response, and primary T-dependent antibody response at a final concentration of 1 ${\mu}g$/ml. They also markedly suppressed the proliferation of lymphocytes induced by lipopolysaccharide, pokeweed mitogen, and concanavaline A at the same concentration. Their suppressive activities, which were comparable to those of cyclosporin A, suggested that they were potent and broad immunotoxic agents on the immune functions of murine lymphocytes.

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Effects of the Administration of water extract of Juglandis Semen without Inner cortex and with Inner cortex on Activity of Splenocytes and Macrophages in Mice (호두 속껍질 없는 것과 있는 것의 물 추출물 투여가 생쥐의 비장세포 및 대식세포의 활성에 미치는 영향)

  • Park, Hoon;Lee, Kyung-A;Kwon, Jin;Ahn, Mun-Saeng;Eun, Jae-Sun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1217-1222
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    • 2006
  • The purpose of this research was to investigate the effects of the administration of Juglandis Semen without inner cortex (JE) or with inner cortex (JEIC) on activity of splenocytes and peritoneal macrophages in BALB/C mice. JE (300 mg/kg, p.o.) did not affect the cell viability of T- and B-lymphocytes in murine splenocytes, but JEIC (300mg/kg, p.o.) increased the cell viability of T- and B-lymphocytes. Furthermore, JE decreased the population of B220$^+$ cells in splenocytes, but JEIC enhanced the population of Thyl$^+$ cells. Also, JEIC enhanced the population of splenic CD4$^+$ cells. JE decreased the production of nitric oxide and the phagocytic activity of peritoneal macrophages, but JEIC increased the production of nitric oxide and the phagocytic activity of peritoneal macrophages. These results suggest that JEIC is more potent than JE against the immune response induced by splenocytes and macrophages.