• IMMUNE NETWORK
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• 제9권3호
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• pp.84-89
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• 2009

The main stream of CD137 studies has been directed to the function of CD137 in $CD8^+$ T-cell immunity, including its anti-tumor activity, and paradoxically the immunosuppressive activity of CD137, which proves to be of a great therapeutic potential for animal models of a variety of autoimmune and inflammatory diseases. Recent studies, however, add complexes to the biology of CD137. Accumulating is evidence supporting that there exists a bidirectional signal transduction pathway for the CD137 receptor and its ligand (CD137L). CD137/CD137L interactions are involved in the network of hematopoietic and nonhematopoietic cells in addition to the well characterized antigen-presenting cell-T cell interactions. Signaling through CD137L plays a critical role in the differentiation of myeloid cells and their cellular activities, suggesting that CD137L signals trigger and sustain inflammation. The overall consequence might be that the amplified inflammation by CD137L enhances the T-cell activity together with CD137 signals by upregulating costimulatory molecules, MHC molecules, cell adhesion molecules, cytokines, and chemokines. Solving this outstanding issue is urgent and will have an important clinical implication.

• 대한한방종양학회지
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• 제4권1호
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• pp.111-129
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• 1998

In order to research the effect of Sipjundaebotang on the immune respons of CD4+ T cell and CD8+ T cell in rats, author have performed this experimental study. Experimental groups are divided into 5 groups(intact, control, sample I, sample II, sample III). Normal group was intact, control group was administrated normal saline 2cc for 5 days, sample I was administrated low concentration of Sipjundaebotang(100/3100pack/ml) 2cc for 5 days, sample II was administrated middle concentration of Sipjundaebotang(500/3100pack/ml) 2cc for 5 days, sample III was administrated high concentration of Sipjundaebotang(2500/3100pack/ml) 2cc for 5 days. WBC, Lymphocyte, CD4+ T cell in the blood, spleen, axillary node and CD8+ T cell in the blood, spleen and axillary node were determined. The results was as follows: 1. WBC count in blood was significantly decrcased in the control, sample I, II, III groups as compared with the normal group. 2. Lymhocyte count in the blood was significantly decreased in the control, sample I, II groups as compared with the normal group. 3. CD4+ T cell count in the blood was significantly increased dose-dependently in the sample I, II, III groups as compared with the normal group. 4. CD4+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. 5. CD4+ T cell count in the axillary node was significantly increased in the sample III group as compared with the normal group, however significantly decreased in the sample I, II groups as compared with the normal group. 6. CD8+ T cell count in the blood was significantly increased in the sample III groups as compared with the normal group. 7. CD8+ T cell count in the spleen was significantly increased in the sample I, II, III groups as compared with the normal group. but there was no differences in the sample groups. 8. CD8+ T cell count in the axillary node was decreased in the sample I, II groups as compared with the normal group.

• 대한약침학회지
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• 제3권2호
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• pp.79-97
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• 2000

Objectives : To investigate the effects of herb-acupunctures of Qi tonification herbs or formula on the rat immune depression induced by an anticancer drug, methotrexate (MTX) Methods: Animals were divided into 5 groups; Normal control group was not given any treatment. Immune depression was induced by oral administration of 1mg/kg MTX b.i.d for 4 days in Control, Sample I, II, and III groups. We treated on CV 4 (Guanyuan) with saline, Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix herb-acupunctures in Control, Sample I, II, and Ill groups, respectively. In both blood and spleen, the assessment of CD4+ T-cell count, CD8+ T-cell count, CD4/CD8 T-cell ratio was performed. Results: Here we show that 3 herb- acupuncture groups have an influence, to some extent, on CD4+ and CD8+ T-cell counts and CD4/CD8 T-cell ratio in both blood and spleen. Astragali Radix herb-acupuncture, in particular, was found to have significantly increased CD4+ T-cell count in blood and CD4/CD8 T-cell ratio in blood and spleen. Conclusions: The results of this study suggest that herb-acupunctures of Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix may have an influence over rat immune depression induced by MTX.

• IMMUNE NETWORK
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• 제3권1호
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• pp.8-15
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• 2003

Background: CD30 is a member of TNF receptor family and expressed on lymphocytes and other hematopoietic cells following activation as well as Hodgkin and Reed-Sternberg cells in Hodgkin's lymphoma. In this study, CD30-mediated regulation of cell adhesion molecule expression on normal activated mouse T cells was investigated. Methods: Mouse T cells were activated with anti-CD3 antibody for induction of CD30, which was cross-linked by immobilized anti-CD30 antibody. Results: High level of CD30 expression on T cells was observed on day 5, but only little on day 3 even under culture condition resulting in an identical T cell proliferation, indicating that CD30 expression requires a prolonged stimulation up to 5 days. Cross-linking of CD30 alone altered neither proliferation nor apoptosis of normal activated T cells. Instead, CD30 appeared to promote cell adherence to culture substrate, and considerably upregulated ICAM-1 and, to a lesser extent, ICAM-2 expression on activated T cells, whereas CD2 and CD18 (LFA-1) expression was not affected. None of cytokines known as main regulators of ICAM-1 expression on tissue cells (IL 4, $IFN{\gamma}$ and $IFN{\alpha}$) enhanced ICAM-1 expression in the absence of CD30 signals. On the other hand, addition of $NF-{\kappa}B$ inhibitor, PDTC (0.1 mM) completely abrogated the CD30-mediated upregulation of ICAM-1 expression, but not CD2 and ICAM-2 expression. Conclusion: This results support that CD30 upregulates ICAM-1 expression of T cell and such regulation is not mediated by higher cytokine production but $NF-{\kappa}B$ activation. Therefore, CD30 may play important roles in T-T or T-B cell interaction through regulation of ICAM-1, and -2 expression.

• 대한한의학회지
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• 제23권1호
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• pp.37-49
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• 2002

Objectives: Maekmoondong-tang and Jeongcheonhwadamgangki-tang are herbal decoctions which have been used as traditional therapeutic agents for asthma. This study was performed to investigate the effects of Maekmoondong-tang and Jeongcheonhwadamgangki-tang on immune Cell & serum OA-specific 19B in broncho-alveolar lavage fluid (BALF) in rat asthma model. Methods: Rats were sensitized with ovalbumin (OA); at day I the sensitized group and Maekmoondong-tang and Jeongcheonhwadamgangki-tang groups were systemically immunized by subcutaneous injection of 1mg OA and 300mg of $Al(OH)_3$ in a total volume of 2ml. At the same time, 1ml of 0.9% saline containing $6{\times}10^9$ B. pertussis bacilli was injected by i.p. for 14 days. After systemic immunization, the rats received local immunization by inhaling 0.9% saline aerosol containing 2% (wt/vol) OA. A day after local immunization, BAL fluid was collected from the rats. A day after local immunization, rats were orally administered with each of Maekmoondong-tang and Jeongcheonhwadamgangki-tang extract for 14 days. Lymphocyte, CD4+T-cell CD8+ T-cell counts, CD4+/CD8+ ratio in BALF, change of serum OA-specific IgE level, and CD4+T-cell CD8+T-cell percentage in the peripheral blood were measured and evaluated. Results: Maekmoondong-tang and Jeongcheonhwadamgangki-tang showed a suppressive effect on the rat asthma model. Maekmoondong-tang decreased total cell, lymphocyte, CD4+T-cell, CD8+T-cell in BALF, and serum OA specific 19B level as compared with the control group, whereas Maekmoondong-tang decreased CD4+/CD8+ ratio in BALF with statistical nonsignificance as compared with the control group. 1 decreased total cell, CD4+T-cell, CD4+/CD8+ ratio in BALF, and serum OA specific IgE level, whereas Jeongcheonhwadamgangki-tang decreased ymphocyte, and CD8+T-cell in BALF with statistical nonsignificance as compared with the control group. CD4+T-cell and CD8+ T-cell percentage in peripheral blood were not changed significantly in all the experimental groups. Conclusions: This study shows that Maekmoondong-tang and Jeongcheonhwadamgangki-tang have a suppressive effect on asthma. Maekmooruiong-tang and Jeongcheonhwadamgangki-tang would be useful asthma treatment agents.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권4호
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• pp.377-383
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• 2021

Purpose: We investigated the association of effector memory (EM) CD8⁺ T cell and CD4⁺ T cell immunity with metabolic syndrome (MS). Methods: Surface and intracellular staining of peripheral blood mononuclear cells was performed. Anti-interleukin-7 receptor-alpha (IL-7Rα) and CX3CR1 antibodies were used to stain the subsets of EM CD8⁺ T cells, while anti-interferon-gamma (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FOXP3) antibodies were used for CD4⁺ T cell subsets. Results: Of the 47 obese children, 11 were female. Children with MS had significantly higher levels of serum insulin (34.8±13.8 vs. 16.4±6.3 µU/mL, p<0.001) and homeostasis model assessment of insulin resistance (8.9±4.1 vs. 3.9±1.5, p<0.001) than children without MS. Children with MS revealed significantly higher frequencies of IL-7Rα^low CD8⁺ T cells (60.1±19.1% vs. 48.4±11.5%, p=0.047) and IL-7Rα^lowCX3CR1⁺ CD8⁺ T cells (53.8±20.1% vs. 41.5±11.9%, p=0.036) than children without MS. As the serum triglyceride levels increased, the frequency of IL-7Rα^lowCX3CR1⁺ and IL-7Rα^highCX3CR1^- CD8⁺ T cells increased and decreased, respectively (r=0.335, p=0.014 and r=-0.350, p=0.010, respectively), in 47 children. However, no CD4⁺ T cell subset parameters were significantly different between children with and without MS. Conclusion: In obese children with MS, the changes in immunity due to changes in EM CD8⁺ T cells might be related to the morbidity of obesity.

• 대한의생명과학회지
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• 제27권4호
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• pp.329-333
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• 2021

We previously identified that tumor cells genetically modified with a 4-1BBL co-stimulatory molecule had anticancer effects in a CT26 mouse colorectal tumor model. To identify the distinction between immune cells in a mouse tumor model treated with tumor cells genetically modified with 4-1BBL or β-gal, we examined the immune cells in CT26-WT, CT26-βgal, and CT26-4-1BBL tumor bearing mice 21 days after tumor cell administration. The CD8+ T cells population in mice treated with tumor cells genetically modified with 4-1BBL was significantly increased on day 21 compared to that of tumor cells genetically modified with β-gal in the spleen and tumor tissue. The CD4+ T cell population was not different between the two mice groups. The Foxp3+CD25^high CD4 T cell population decreased on day 21 in tumor tissues, but the decrease was not significant. We also found that CD8 T cells had pivotal roles in inhibiting tumor growth by treating mice with ant-CD4 and CD8 antibodies. These results suggest that tumor cells genetically modified with 4-1BBL could inhibit tumor growth by affecting on CD8 T lymphocytes.

• 동의생리병리학회지
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• 제20권6호
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• pp.1576-1583
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• 2006

In order to investigate the effect of Goamshimshinhwan(GASSW) on SD rats with deteriorated immunity caused by methotrexate. Methotrexate was fed to the SD rats once a day for 4 days. After the immune responses of the at a dosage 1,000, 500 and 250mg/kg/10ml. and the changes on body weight and gains, spleen weight, total blood leukocyte numbers, total lymphocyte numbers, the percentage of B-cell, T-cell, CD3+CD+4 T-cell, CD3+CD8+ T-cell and CD4+/CD8+ T-cell ratios in the bolld and spleen were observed. In addition, the serum IL-2 levels and productivity of IL-2 of splenic cells were also demonstrated in this study. The changes on body weight were increased significantly in 100 and 500mg/kg of GASSW groups and the changes on body gain were increased significantly in 1000mg/kg of GASSW groups as compared with control group. The changes on the spleen weight (absolutely or relatively) were increased significantly in all GASSW groups as compared with control group. The total blood leukocyte numbers were increased significantly in 1000 and 500mg/kg of GASSW groups as compared with control group. The total lymphocyte numbers were increased significantly in all GASSW groups in the blood and increased significantly in 1000 and 500mg/kg of GASSW goups in spleen as compared with control group. The percentage of B-cell and T-cell were increased significantly in 1000mg/kg of GASSW groups in the blood and increased significantly in 1000 and 500mg/kg of GASSW groups in spleen as compared with control group. The percentage of CD3+CD4+ T-cell and the serum IL-2 levels and productivity of IL-2 of splenic cells were increased significantly in 100 and 500 mg/kg of GASSW groups in the blood and spleen as compared with control group. The percentage of CD3+CD8+ T-cell were increased significantly in 1000mg/kg of GASSW groups only in spleen as compared with control groups. The CD4+/CD8+ T-cell ratios were increased significantly in 1000 and 500mg/kg of GASSW groups only in the blood as compared with control group. Goamshimshinhwan(GASSW) has immuno-stimulating effect on SD rats with deteriorated immunity caused by methotrexate.

• Journal of Microbiology and Biotechnology
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• 제27권6호
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• pp.1189-1197
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• 2017

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of $CD8^+$ T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of $CD8^+$ T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and $IFN-{\gamma}$ as the $CD8^+$ T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain ($IL-2R{\alpha}$) on $CD8^+$ T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, $IFN-{\gamma}$, and CD69 on $CD8^+$ T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of $IL-2R{\alpha}$ expression in $CD8^+$ T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

• 한국가축번식학회지
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• 제27권3호
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• pp.225-231
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• 2003

본 연구는 생체 내 세포 및 조직배양기로서의 면역결핍동물을 개발할 목적으로 proximal lck promoter와 DT-A gene를 이용하여 형질전환생쥐을 생산하고 이 형질전환생쥐의 면역세포에서 DT-A gene이 발현되는지를 분석하였다. 형질전환생쥐와 정상생쥐로부터 thymus, spleen 및 liver에서 RNA를 추출하여 RT-PCR수행하였는데 정상생쥐의 조직에서는 어떠한 DT-A gene의 발현양상을 얻을 수 없었으나 형질전환생쥐의 thymus, spleen, liver에 DT gene의 발현을 확인할 수 있었고, Northern blotting을 이용하여 형질전환생쥐의 thymus, spleen 및 liver에서 DT-A gene이 강하게 발현되는 것으로 나타났다. 형질전환생쥐 $F_1$ 및 $F_2$ 산자의 혈액에서 T-cell 발달의 분포도를 확인하기 위해 CD4 및 CD8 antibody를 이용하여 FACS analysis를 실시하였는데 형질전환생쥐의 혈액 내 mature T-cell인 single positive thymocyte의 수가 정상생쥐에 비해 감소하는 경향을 나타냈다. 정상생쥐의 혈액 내 T-cell 중 $CD8^{+}$ T-cell의 경우 약 50%를 나타냈으나 형질전환생쥐의 경우 33%로 감소하였고, $CD4^{+}$ T-cell은 정상생쥐에서 10%를 차지하고 있으나 형질전환생쥐에서는 5.9%로 감소되는 것으로 분석되었다. 그러므로 본 연구의 형질전환생쥐에서 lck promoter에 의해 초기 immature한 상태의 T-cell에서 DT-A gene이 발현되어 발육중인 T-cell이 파괴 되어 mature 상태인 $CD4^{+}CD8^{-}$나 $CD4^{-}CD8^{+}$ cells (single-positive)들이 감소된 것으로 확인되었다.