• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2027-2030
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• 2016

Objective: To investigate the effect of peripheral blood CD4 + CD25 + regulatory T cell on postoperative immunotherapy in patients with renal carcinoma. Methods: 38 patients with renal cell carcinoma were recruited, and 20 patients from the operation group purely underwent the radical nephrectomy therapy, 18 patients from the combined group successively underwent the radical nephrectomy therapy and IFN-${\alpha}$ adjuvant immunotherapy. Additionally, 12 healthy subjects were recruited in the same period of time and regarded as the control group. Flow cytometry was used to detect CD4 +, CD8 +, CD4 + CD25+ T lymphocyte subset content and the ratio of all parts in the pre-operative period, in the first post-operative week and in the third post-operative month, compare and analyze its variation trend. Results: The CD4+CD25+ T lymphocyte subset content of individual renal carcinoma patients was significantly higher than that of the control group, also increases with the progression in the tumor stage (P<0.05). The post-operative CD4 + CD25+T lymphocytes of individual operation group and combined group patients showed different degrees of increment, but the increment of the combined group was significantly lower than that of the operation group (P<0.05). For the combined group patients with less pre-operative CD4 + CD25+T lymphocytes, their levels would increase after the immunotherapy, while the pre-operative patients with more CD4 + CD25+ T lymphocytes were the opposite situation. Conclusion: The detection of peripheral blood CD4+CD25+ regulatory T lymphocyte subset can reflect the anti-tumor immune status of renal cell carcinoma patient body. It can contribute to predict the prognosis of immunotherapy and provide reference for the choice of renal carcinoma post-operative adjuvant immunotherapy.

• Journal of Oral Medicine and Pain
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• 제34권4호
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• pp.363-369
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• 2009

미란형 구강편평태선과 재발성 아프타성 구내염은 T림프구에 의해 매개되는 염증성 면역질환이다. T림프구에 영향을 주는 다양한 조절 인자들 중 CD28, CD45, CD152, CD154, CD279등의 mRNA가 미란형 구강편평태선 및 재발성 아프타성 구내염 환자들의 비자극성 전타액내에서 어떻게 발현되는지를 살펴보고, 이것의 진단학적 가치를 평가하고자 한다. 미란형 구강편평태선으로 진단받은 환자군 18명, 재발성 아프타성 구내염으로 진단받은 환자군 12명, 정상군 8명에게서 비자극성 전타액을 10분간 채득한 후, 상피세포를 분리하여 mRNA를 추출하였다. Real time PCR을 이용하여 각 군의 T림프구 조절 인자들의 mRNA 발현 양상을 비교분석하였다. 미란형 구강편평태선의 T림프구 조절인자들의 mRNA 발현 양상은 정상인과 비교 결과, CD45, CD279는 높게 측정되었고, CD154는 낮게 측정되었다. 재발성 아프타성 구내염 환자들의 T림프구 조절인자들의 mRNA 발현 양상은 정상인과 비교 결과, CD45, CD279는 높게 발현되었고, CD28, CD154는 낮게 발현되었다. 부가적으로 미란형 구강편평태선 환자군의 타액내 CD152의 발현 양상은 재발성 아프타성 구내염 환자군보다 높게 발현되었다. 미란형 구강편평태선과 재발성 아프타성 구내염 환자들의 비자극성 전타액내 T림프구 조절인자들의 mRNA 발현 양상은 각 질환의 진단에 기여할 수 있을 것으로 사료된다.

• 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.

• 약학회지
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• 제35권3호
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• pp.154-164
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• 1991

These experiments were conducted to investigate the effects of Glycyrrhizae Radix extract(GR) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [$^{3}$H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}Ca^{2+}$ to P388D$_{1}$ cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GR(10$^{-3}$g/ml). Histamine production in mouse spleen cell culture was significantly increased by 48 hour incubation added 0.25$\mu\textrm{g}$/ml of Con A. Con A-dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 $\mu\textrm{g}$/ml of Con A. GR depressed histamine contents at 10$^{-9}$~10$^{-4}$g/ml. and Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-5}$~10$^{-4}$g/ml. IL-1 activity was significantly decreased by 10$^{-8}$~10$^{-4}$g/ml of GR. $Ca^{2+}$ uptake was not changed by GR, but antibody production markedly increased at 10.0~50.0 mg/kg of GR. From the above results, it is suggested that GR have immuno-regulatory action; GR decreased cell-mediated immune response and increased antibody production by B lymphocyte at high doses.

• 미생물학회지
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• 제49권3호
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• pp.221-227
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• 2013

인간면역결핍바이러스(Human immunodeficiency virus; HIV), B형 간염 바이러스(Hepatitis B virus; HBV), 그리고 C형 간염 바이러스(Hepatitis C virus; HCV)는 만성 감염질환을 일으키는 대표적인 바이러스들이다. 인체내 감염시 임상적 진행경과에 따른 바이러스 특이 T림프구의 항바이러스 기능변화 및 바이러스의 체내 지속성과 T림프구에 발현되는 다양한 면역인자(e.g., CD28, CD25, FoxP3, PD-1, CTLA-4)들과의 구체적인 상관관계는 최근 많은 국내외 연구진들을 통해 연구되고 있다. 그 중 FoxP3 (forkhead box P3), PD-1 (programmed death-1) 그리고 CTLA-4 (cytotoxic T lymphocyte-associated antigen 4)는 T림프구에서 발현되는 면역조절인자로 만성 바이러스성 감염시 그 발현이 증가되는 것으로 관찰되었으며, 항바이러스 작용을 가지는 T림프구의 기능결핍과 밀접한 상관관계가 있는 것으로 알려져 있다. 본 총설에서는 만성적인 HIV, HBV, 그리고 HCV 감염에서 바이러스 특이 T림프구에서 발현되는 FoxP3, PD1, 그리고 CTLA-4의 발현변화와 각 질환의 임상적 진행경과와의 상관성, 그리고 이들 발현이 T림프구의 항바이러스 기능에 미치는 영향 등을 중심으로 기술하였다.

• 약학회지
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• 제35권3호
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• pp.174-181
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• 1991

These experiments were conducted to investigate the effects of glycyrrhizin(GL) and glycyrrhetinic acid(GA) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [sup 3/H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}$Ca$^{2+}$ to P388D$_{1}$, cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GL(10$^{-3}$M) and GA(10$^{-4}$M). Histamine production in mouse spleen cell culture was significantly increased by the addition of 0.25 $\mu\textrm{g}$/ml of Con A, after 48 hour incubation. Con A dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 .mu.g/ml of Con A. The effects of GL on histamine contents and T-lymphocyte proliferation were significantly decreased at high dose (10$^{-5}$M), while IL-1 activity was remarkably suppressed by 10$^{-8}$~10$^{-4}$M of GL. $Ca^{2+}$ uptake was not changed, but antibody production was increased by GL(10 mg/kg). GA inhibited histamine contents at 10$^{-9}$~10$^{-7}$ and depressed Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-7}$~10$^{-5}$M of GA, but increased suboptimal dose (Con A 0.1 $\mu\textrm{g}$/ml) at 10$^{-9}$~10$^{-7}$M of GA. IL-1 activity was suppressed by 10$^{-8}$~10$^{-4}$M of GA and $Ca^{2+}$ uptake was enhanced by 10$^{-9}$~10$^{-6}$ of GA, but antibody production was not changed by GA. From the above results, it is suggested that GL and GA have immuno-regulatory action. GL decreased cell-mediated immune response, and increased humoral immune response at high dose. On the other hand, low dose of GA enhanced cell-mediated immune response, while high doses of GA decreased humoral immune reaction.

• 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.

• 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 Periodontal and Implant Science
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• 제27권4호
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• pp.805-818
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• 1997

Immune responses of periodontal tissue may be regulated by products of sensory afferent nerve endings such as neuropeptides. Substance P(SP), a tachykinin neuropeptide, has been previously reported to stimulate the activities of T lymphocyte. Therefore, I examined the role of SP in IL-2 production and cell proliferation by using a homogeneous line of T lymphocytes(Jurkat and HuT78). Cell proliferation rate was determined by [$^3H$]-thymidine incorporation test, and IL-2 was quantitated by the growth rate of CD4+ IL-2-dependent T lymphocyte line CTLL-2. SP stimulated cell proliferation of T lymphocytes at the concentration of $10^{-12}$ and $10^{-8}$M in a biphasic bell-shape dose-dependent manner. However, SP alone did not induce IL-2 release at the concentration range of $10^{-6}$ to $10^{-14}$M. The upregulation of IL-2 release was observed when $10^{-12}$M SP was applied together with mitogens such as Con A or PHA+PMA on T cell lines, especially on Jurkat. Con A or PHA+PMA demonstrated to increase the rate of cell proliferation of Jurkat, which had shown to produce much amount of IL-2 indicating that mitogen-induced cell proliferation might be partially influenced by released IL-2. It was concluded that regulatory effects of SP on the immune/inflammatory response could be mediated through the costimulatory upregulation of IL-2 production and increase of cell proliferation of T lymphocyte.

• 한국약용작물학회지
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• 제10권5호
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• pp.327-332
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• 2002

This study was conducted to investigate the immuno-regulatory effect and apoptosis of L1210 and HL60 leukemia cells of methanol-extracts of Cornus kousa Burg(CKB). The proliferation of mouse splenocytes and thymocytes enhanced by the addition of $10\;{\mu}g/ml$ of CKB. CKB were administered p.o. once a day for 7 days in adult male BALB/c mice. CKB increased the splenic and thymic T lymphocytes, especially the number of $T_H$ cells markedly increased by the treatment of CKB. CKB treatment induced the apoptotic cell death in L1210 mouse leukemia and HL60 human leukemia cells. In addition, CKB also accelerated the phagocytic activity in peritoneal macrophages and increased the production of plaque forming cells. These results suggest that CKB have an various immuno-regulatory property.