• 동국한의학연구소논문집
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• 제6권2호
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• pp.99-107
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• 1998

본 실험은 cyclosporin A(CsA)에 의한 시간의 경과에 따른 림프절에서의 세포성 면역억제를 조사하기 위해서 시행된 것으로 BALB/C계 생쥐에 10일동안 CsA(45mg/kg/day) 투여 후 림프절에서의 T 림프구, IL-2 수용기 그리고 자연살해(NK)세포의 분포 변화를 관찰하였다. 대조군의 림프절에서는 L3T4(CD4)에 양성반응을 보이는 도움 T림프구, Ly2(CD8)에 양성반응을 보이는 세포독성 T 림프구 그리고 CD25R에 양성반응을 보이는 IL-2 수용기를 가진 세포는 곁피질(paracortex)과 수질동(medullary sinus)에서 분포하였다. CsA 투여 후 처음 3일까지는 이들 양성반응세포의 분포 변화는 없었으며 양성반응성의 변화도 없었다. 그러나 CsA 투여 7일부터 양성반응 세포수의 감소와 양성반응성의 약화가 관찰되기 시작하였으며 이러한 변화는 시간이 경과하여 14일에 이르렀을 때 가장 큰 감소추세로 나타났다. 한편 NK1.1(CD56)에 양성반응을 보이는 자연살해세포는 피질과 수질에 분포하였으며 CsA 투여 후 시간의 경과에 따라 양성반응 세포수가 감소하였으며, 이러한 감소는 14일에서 가장 큰 것으로 나타났다. 이상의 결과로 미루어보아 CsA 투여는 림프절에서의 IL-2 분비저해를 통해 T 림프구와 NK세포의 활성을 차단하여 선택적이면서 효과적인 세포성 면역억제작용을 하고 있는 것으로 사료된다.

• 대한한방소아과학회지
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• 제21권2호
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• pp.13-34
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• 2007

Objectives The purpose of this study is to examine of the effect of SPAR medicines on the atopy eruption control Methods This experiment is about the expression of IgE, IL-4, IL-6, IL_13, IgM, IgG2a, IgG2b, IgG1 level in serum, and $IFN-{\gamma}$ production by SPAR medicines. We assayed for $CD3e^+/CD69^+$, $CD044^+/CD19^+$ positive cells by flow cytometry in splenocytes and observed the revelation of $CD3e^+/CD69^+$, $CD4^+/CD8^+$, $CD44^+/CD19^+$ marker in PBMC, spleen and DLN. We also observed the outturn of IL-4, IL-5, CCR3, $IFN-{\gamma}$ in skin of a NC/Nga mice. We also analyzed NC/Nga mice's ear and neck-back skin after biopsy and dye by H&E staining method, measured about epidermis and dermis part in comparison with control group. Results SPAR medicines as treatment result to a NC/Nga mice, clinical skin severity score decreased remarkably than the ontrol group. Specially, experiment was results by measuring IgE and IL-6 content in serum 8 weeks, 10 weeks, 12 weeks, 16 weeks, 20 weeks respectively, and it was decreased remarkably than the control group. After experiment ended, the result that observed the revelation CD3e, CD4, CD8, CD19, CD69, CD11a marker in lymph node establishment were observed and that B/T rate becomes recover as normal with political background. In addition to that, the control group was decreased in the measured value of IL-4, IL-5, IL-13, IgM, IgG2a, IgG1's level in serum, and $IFN-{\gamma}$' production secreted in Th1 cell displayed increase by SPAR medicines. IL-4, IL-5, CCR3, and $IFN-{\gamma}$'s gene revelation amount displayed marked decrease than the control group in result that observe effect that get in skin of a NC/Nga dermatitis mouse. Moreover in culture supernatant which cultivate for 14 days after separate skin cell, IL-13 and IL-6 production, and $CD69^+/CD3e^+$, $CD44^+/CD19^+$ expression cell number was decreased than the control group's number. Course inflammation immunocyte permeated of result that effect that SPAR medicines get to NC/Nga mice's skin establishment analyzes ear and neck-back skin after biopsy, and dye by H&E method decreased about epidermis and inflammation of dermis part remarkably than the control group. Conclusions Th1 cell and Th2 cell observe to be shifted by secretion amount of IL-4 and $IFN-{\gamma}$ by SPAR medicines could know that SPAR medicines can be use for treatung allergy autoimmune disease.

• IMMUNE NETWORK
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• 제2권1호
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• pp.35-40
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• 2002

Background: CTLA-4 (Cytotoxic T Lymphocyte associated Antigen 4, CD152) has been known as a homologue of CD28, an accessory molecule providing a key costimulatory signal for successful antigen-driven activations of T lymphocyte. Most of biochemical and cell biological characteristics of the CD152 protein remain unknown while those of CD28 have been characterized in detail. Methods: In this study CD152 expression in both $CD4^+$ and $CD8^+$ PBLs was studied by using flow cytometry. And intracellular CD152 multiprotein complex was purified and used for generating antibodies recognizing proteins composing of intracellular CTLA-4 multi protein complex. Results: Level of surface expression of this molecule was peaked at 2 days of PHA stimulation in flow cytometric analysis. 40~45% of PHA blast cells were $CD152^+$ in both of two subsets at this stage and the level of expression were equivalent in both two subsets. Contrary to this surface expression, intracellular expression was peaked at day 3 and it was preferentially induced in $CD8^+$ cells and about 60% of $CD8^+$ cells were $CD152^+$ at this stage. High molecular weight (>350 kD) intacellular CD152 protein complex purified by using preparative electrophoresis were immunized into rabbits and then 3 different anti-P34PC4, anti-P34PC7 and anti-P34PC8 antibodies were obtained. Using these 3 antibodies two unknown antigens associated with intracellular CD152 multiprotein complex were found and their molecular weights were 54 kD and 75 kD, respectively. Among these, the former was present as 110 kD homodimer in non-reducing condition. Conclusion: It seemed that 34 kD intracellular CD152 molecule forms high molecular weight multiprotein complex at least with 2 proteins of 75 kD monomer and 110 kD homodimer.

• IMMUNE NETWORK
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• 제10권4호
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• pp.120-125
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• 2010

Dysfunction of the virus-specific T cells is a cardinal feature in chronic persistent viral infections such as one caused by hepatitis C virus (HCV). In chronic HCV infection, virus-specific dysfunctional CD8 T cells often overexpress various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be overexpressed in functionally impaired T cells. The roles of other inhibitory receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in chronic HCV patients. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.

• Journal of Periodontal and Implant Science
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• 제44권5호
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• pp.235-241
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• 2014

Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which $CD103^+$ DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived $CD103^+$ DCs to promote the differentiation of antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from $CD14^+$ monocytes from the PBMCs of 10 healthy subjects. Once the $CD103^+$ DCs were purified, the cell population was enriched by adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were synthesized to pulse $CD103^+$ DCs as a tool for presenting the peptide antigens to stimulate $CD3^+$ T cells that were isolated from human PBMC. Exogenous interleukin 2 was added as a coculture supplement. The antigen-specific T-cell lines established were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity to stimulate peptide-specific Tregs, whereas $CD103^+$ DCs showed a potent antigen presenting capability to promote the peptide-specific Tregs, especially for peptide 14. RA enhanced the conversion of $CD103^+$ DCs, which paralleled the antigen-specific Treg-stimulating effect, though the differences failed to reach statistical significance. Conclusions: We demonstrated that $CD103^+$ DCs can promote antigen-specific Tregs from naive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was an effective reagent that induces mature DCs with the typical phenotypic expression of CD103 that demonstrated the functional capability to promote antigen-specific Tregs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3137-3140
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• 2015

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

• Journal of Ginseng Research
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• 제48권1호
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• pp.68-76
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• 2024

Background: Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. Methods: This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. Results: All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4⁺ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4⁺ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28^- subset was ameliorated. Conclusions: These findings suggest that KRG promotes the repopulation of CD4⁺ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.

• 약학회지
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• 제46권3호
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• pp.213-218
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• 2002

In the previous report, we described the in vivo antitumor activity of PJ-4, a protein-polysaccharide fraction prepared from the culture filtrate of an insect-born fungus, Paecilomyces tenuipes DGUM 32001. In the present study, we elucidated the immunomodulating activity of PJ-4 on the BALB/c mouse splenic lymphocytes using flow cytometrical techniques. As a result, PJ-4 was found to stimulate the lymphocytes not only to form lymphoblasts but also to express CD25 (IL-2 receptor $\alpha$ chain) molecule, which is well known as a T cell activation marker. More interestingly, its T cell stimulatory activity was more strongly exerted on CD8$^{+}$ T cells than on CD4$^{+}$ T cells. All these data suggest that PJ-4 exerts its antitumor activity at least partly through stimulation of T cells which play major roles in the cell-mediated immune system.tem.

• Journal of Nutrition and Health
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• 제43권2호
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• pp.152-160
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• 2010

본 연구에서는 노화에 따른 영양 태와 면역지표의 변화를 알아보기 위해 연령대가 다른 성인 여성 총 54명을 대상으로 실시하였다. 연령 이외의 환경적 유전적 차이를 최소화하기 위하여 대부분이 한 가족 내 3세대, 즉 20대인 딸, 40~50대인 어머니, 60세 이상의 할머니들로 구성시켰다. 대상자들의 신체 계측, 식이 섭취 조사, 생화학적 검사를 통해 영양상태를 판정하였고, 면역지표를 평가하기 위해 총 백혈구 수 및 백혈구 백분율을 측정하였다. 또한 세포매개성 면역능력을 측정하기 위해 T ltmphocyte과 CD4 +, CD8 + 그리고 NK cells의 수와 비율을 측정하였으며 체액성 면역지표를 알아보기 위해 면역 글로불린 G, A, M의 농도를 측정하였다. 신체 계측 결과 연령이 증가됨에 따라 평균 체지방 함량은 증가하였고 체내 총 수분량과 근육의 양은 줄어드는 경향을 나타냈다. 각 연령별 영양 섭취 상태를 조사한 결과 20대 여대생군의 경우 열량과 철분을 제외한 다른 영양소의 영양상태는 비교적 양호하였으나 3대 영양소의 열량 섭취 비율 또한 한국인 영양섭취기준과 거의 일치하는 것으로 나타났다. 40~50대 어머니군에서도 철분의 영양 상태가 권장량에 비해 부족하였고, 할머니군에서는 에너지 섭취량은 권장량에 비해 낮은 반면 단백질과 철분의 섭취량은 양호한 것으로 나타났다. 총 백혈구 수 및 백혈구 백분율은 조사 대상자 대부분이 정상 범위에 속해 연령 증가에 따른 유의성이 없었으며, T lymphocyte 및 CD4 +, CD8 +와 NK cells을 조사한 결과 T lymphocyte과 CD4 + T cells은 연령 증가에 따라 유의적 차를 보이지 않는 반면 CD8 + T cells은 연령이 증가할수록 유의적으로 감소하여 CD4 +：CD8 +의 비율이 노화됨에 따라 증가하는 경향을 나타냈고, 전체 lymphocyte 중에서 NK cells과 B lymphocyte 수는 유의적 차를 보이지 않았으나 면역 글로불린 M은 노화에 따라 그 농도가 감소하는데 비해 면역 글로불린 A는 각 군별 유의성이 없었고, 면역 글로불린 G는 어머니군에서 유의적으로 높았다. 영양 면역학은 비교적 최근의 관심 분야이고 더욱이 국내에서 이 분야의 연구는 매우 미흡한 실정이다. 그러므로 급속히 발달하고 있는 면역학 이론의 올바른 이해와 새로운 연구 방법의 신속한 적용, 정확한 연구 결과의 해석으로 좀더 구체적이고 체계적인 연구를 통해 각 영양소가 인체 면역지표에 미치는 구체적 메커니즘을 밝히고 면역능 증진을 위한 생리적 활성을 줄 수 있는 각 영양소의 권장량에 대한 연구가 앞으로 이루어져야 할 것으로 보인다.

• 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.