• 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.

• Molecules and Cells
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• 제37권1호
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• IMMUNE NETWORK
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• 제8권4호
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• pp.107-123
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• 2008

It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4329-4333
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• 2015

Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derived suppressor cells (MDSCs) after treatment of cisplatin (DDP) in A375 human melanoma model. Materials and Methods: BALB/c nude mice were inoculated with A375 cells to establish the human melanoma model and randomly divided into control group given normal saline (NS) and experimental group treated with DDP (5 mg/kg). The percentages of MDSCs in the tumor tissue and peripheral blood after DDP treatment were detected by flow cytometry. The proliferation and interferon-${\gamma}$ (IFN-${\gamma}$) secretion of T cells co-cultured with MDSCs were analyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot (ELISPOT) assay, respectively. Results: In A375 human melanoma model, DDP treatment could significantly decrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheral blood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-cultured with DDP-treated MDSCs could dramatically elevate the proliferation and production of INF-${\gamma}$. Conclusions: DDP can decrease the frequency and attenuate immuno-inhibitory function of MDSCs in A375 melanoma model, suggesting a potential strategy to augment the efficacy of combined immunotherapy.

• 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.

• Biomolecules & Therapeutics
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• 제28권1호
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• pp.1-17
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• 2020

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exert suppressive function on the immune response. MDSCs expand in tumor-bearing hosts or in the tumor microenvironment and suppress T cell responses via various mechanisms, whereas a reduction in their activities has been observed in autoimmune diseases or infections. It has been reported that the symptoms of various diseases, including malignant tumors, can be alleviated by targeting MDSCs. Moreover, MDSCs can contribute to patient resistance to therapy using immune checkpoint inhibitors. In line with these therapeutic approaches, diverse oligonucleotide-based molecules and small molecules have been evaluated for their therapeutic efficacy in several disease models via the modulation of MDSC activity. In the current review, MDSC-targeting oligonucleotides and small molecules are briefly summarized, and we highlight the immunomodulatory effects on MDSCs in a variety of disease models and the application of MDSC-targeting molecules for immuno-oncologic therapy.

• IMMUNE NETWORK
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• 제9권6호
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• pp.209-235
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• 2009

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is a clear rationale for developing clinical strategies to diminish their regulatory influences, with the ultimate goal of augmenting antitimor immunity. Therefore, manipulation of Treg cells represent new strategies for cancer treatment. In this Review, I will summarize and review the explosive recent studies demonstrating that Treg cells are increased in patients with malignancies and restoration of antitumor immunity in mice and humans by depletion or reduction of Treg cells. In addition, I will discuss both the prognostic value of Treg cells in tumor progression in tumor-bearing hosts and the rationale for strategies for therapeutic vaccination and immunotherapeutic targeting of Treg cells with drugs and microRNA.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.388-394
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• 2009

The cytokines which is produced by allergen-specific T helper (Th) cells play a pivotal role in the pathogenesis of asthma. Asthma is caused by exaggerated T-helper 2 (Th2)-based immune responses. It is suggested that controlling such Th2-based response is necessary for asthma therapy. The current therapies for asthma focus primarily on control of symptoms and suppression of inflammation, without affecting the underlying cause. So, we examined that anti-asthmatic drugs might have play a certain role in Th2/Th1 balance. Splenocytes isolated from ovalbumin (OVA)-sensitized mice cultured with anti-asthmatic drugs. It is well known that Th2 and Th1 immune responses can balance one another, as Th2 mediators suppress Th1 responses and Th1 mediators similarly inhibit Th2 responses. But salmeterol inhibits both of Th1 and Th2 mediators, which salmeterol is a suppressor of immune responses not only a suppressor of Th2-based immune responses. Aminophylline is a weak suppressor of immune responses. But ipratropium and cromoglycate don't have any suppressor effect to Th2-driven responses. They only have suppressor effect to Th1 immune responses. Salmeterol, ipratropium, aminophylline, and cromoglycate augmented mRNA levels of CRTH2, EP2, and IP2 receptors in OVA-sensitized splenocytes. It is well known that the up-regulation of CRTH2 - $PGD_2$ receptor - results in restraint of eosinophil recruitment and that the increment of IP and EP2 - $PGI_2$ and $PGE_2$ receptor, respectively - may induce the accumulation of cAMP that decrease the effector function of T cells. Moreover salmeterol and cromoglycate increase the mRNA expression of $PGD_2$ synthase. These findings indicate that anti-asthma agents may alleviate the immunological responses that cause the asthmatic diseases.

• 생명과학회지
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• 제19권8호
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• pp.1164-1169
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• 2009

비정상적 DNA메칠화는 암 발생에 있어 중요한 역할을 한다. 최근 연구에 의하면 암줄기세포 유지에 있어 DNA과메칠화가 연관되어 있다고 보고하고 있다. 따라서 본 연구는 4T1 유방암 실험모델에서 demethylating agent인 AZA 처리에 따른 후성유전적 변화가 암줄기세포의 유지 및 증식에 있어 어떠한 영향을 미치는지 조사 하였다. 4T1 세포에서 AZA 처리에 따른 tumorsphere 형성이 감소 하는 것을 in vitro 실험을 통해 관찰 하였고, in vivo 실험에서는 줄기세포 조절 유전자들 (Oct-4, Nanog. Sox2)의 발현이 감소 되는 것을 확인 하였다. 본 연구 결과로 볼 때 4T1 유방암 실험모델에서 AZA에 의한 후성유전적 변화는 줄기세포 조절 유전자(SRG)들의 발현을 조절하면서 암줄기세포 특성을 변화시켜 암줄기세포의 증식 및 유지를 억제 할 것으로 사료된다. 향후 이러한 DNA 메칠화 억제를 항암치료에 응용하면, 암줄기세포를 파괴함으로써 암의 재발 및 악성화를 효과적으로 제어 할 수 있을 것으로 사료된다.

• 생명과학회지
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• 제27권8호
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• pp.951-957
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• 2017

후박은 전통적으로 동양의학에서 사용되어왔는데 인간 급성 백혈병 세포주인 Jurkat T 세포를 사용하여 후박의 세포독성 관련 기작을 알아보았다. 후박 뿌리(3 kg)를 메탄올로 추출, 증류한 후 내용물을 물에 녹여 동결 건조 후 사용 하였다. 그 활성물질을 MTWE이라 명명하였다. MTWE을 0, 25, 50, $100{\mu}g/ml$의 농도로 처리하고 세포사멸 과정을 보았다. 즉, mitochondria cytochrome c 방출, caspase-3의 활성화 및 ICAD 분해를 관찰하였다. 더욱이, mitochondria cytochrome c 방출 억제자인 Bcl-xL이 발현이 감소되는 것을 Jurkat T 세포에서는 확인하였다. 이러한 결과는 MTWE가 mitochondria 신호전달 과정을 통해서 세포사멸을 유도 한다고 할 수 있다. 또한, MTWE를 0, 25, 50, $100{\mu}g/ml$ 처리에 대한 암세포 성장억제인자인 DUSP6가 증가되는 것을 확인하였고 핵의 apoptotic morphology 변화를 DAPI를 통해 관찰할 수 있었다. 비록 DUSP6와 다른 관련인자들간의 관련성을 찾아야 하지만, 이상의 결과는 MTWE가 T세포에 의한 급성 백혈병을 조절하는데 이용 될 수 있다는 것의 의미한다.