• 대한수의학회지
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• 제52권3호
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• pp.183-191
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• 2012

The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require $CD4^{+}CD25^{+}$ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.

• IMMUNE NETWORK
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• 제21권5호
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

• 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.

• 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.

• Restorative Dentistry and Endodontics
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• 제27권1호
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• pp.1-11
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• 2002

Immune responses associated with bacterial infection involve various inflammatory cells. Clinical symptoms and pathologic features are particularly influenced by the predominant cells Among inflammatory cells, T cells have the heterogenity. T cells may develop into the mature cells expressing the cell surface markers with different functions and T helper cells are categorized into Th1 and Th2 cells based on their different patterns of cytokine production. The objective of this study was to investigate the change of expression of surface markers on T cells and the Th1/Th2 immune response in pulpal inflammation associated with specific bacteria. We experimentally induced pulpal inflammation in rat incisors by drilling without coolant and innoculated with Streptococcus mutans (S.M. group), Porphyromonas endodontalis (P.E. group), or only sterile cotton (control group). After 1, 2, and 5 days, mandibular incisors were extracted and the pulp tissues were extirpated The expressions of IL-2 recepters (CD25) and ICAM-1 (CD54) on CD4+ and CD8+ cells in the pulps were determined using a flow cytometer, and the concentration of IL-2, IFN-$\gamma$ and IL-4 was measured by enzyme-linked immunosorbent assay. The results were as follows: 1 In the S.M. group, CD4+ cells were more increased at 2nd day than 1st day and in the P.E. group, CD8+ cells were more increased at 2nd day than 1st day. 2. The percentages of CD4+, CD4+25+ and CD4+54+ cells were decreased in the pulp tissues at 5th day after irritation in all groups. 3. The ratios of CD4+/CD8+, CD4+/CD4+25+ and CD4+/CD4+54+ in the pulps at 2nd day after irritation by P. endodontalis were significantly lower than the other groups. 4. The higher concentrations of IFN-$\gamma$ than IL-4 in the pulps at 2nd day after irritation by P. endodontalis showed that T helper 1 reaction were predominant in the early stage of the pulpal inflammation induced by P. endodontalis. 5. The higher concentrations of IL-4 than IFN-$\gamma$ in the pulps at 1st day and 5th day after irritation by S. mutans were measured but the differences were not significant.

• IMMUNE NETWORK
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• 제23권3호
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• pp.25.1-25.15
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• 2023

Mucosal environments harbour lymphocytes, which express several adhesion molecules, including intestinal homing receptors and integrin αE/β7 (CD103). CD103 binds E-cadherin, an integrin receptor expressed in intestinal endothelial cells. Its expression not only enables homing or retention of T lymphocytes at these sites but is also associated with increased T lymphocyte activation. However, it is not yet clear how CD103 expression is related to the clinical staging of breast cancer, which is determined by factors such as the size of the tumor (T), the involvement of nearby lymph nodes (N), and presence of metastasis (M). We examined the prognostic significance of CD103 by FACS in 53 breast cancer patients and 46 healthy controls enrolled, and investigated its expression, which contributes to lymphocyte recruitment in tumor tissue. Patients with breast cancer showed increased frequencies of CD103⁺, CD4⁺CD103⁺, and CD8⁺CD103⁺ cells compared to controls. CD103 was expressed at a high level on the surfaces of tumor-infiltrating lymphocytes in patients with breast cancer. Its expression in peripheral blood was not correlated with clinical TNM stage. To determine the localisation of CD103⁺ cells in breast tissue, tissue sections of breast tumors were stained for CD103. In tissue sections of breast tumors stained for CD103, its expression in T lymphocytes was higher compared to normal breast tissue. In addition, CD103⁺ cells expressed higher levels of receptors for inflammatory chemokines, compared to CD103^- cells. CD103⁺ cells in peripheral blood and tumor tissue might be an important source of tumor-infiltrating lymphocyte trafficking, homing, and retention in cancer patients.

• 한국미생물·생명공학회지
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• 제37권2호
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• pp.160-169
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• 2009

$\gamma$-PGA는 우리 전통 콩 발효식품인 청국장의 끈적끈적한 점액성의 성분으로, 매우 다양한 기능을 가지고 있는 천연 소재이다. 이러한 $\gamma$-PGA가 아토피발진 억제 가능성을 알아보기 위해 NC/Nga 생쥐를 사용하여 in vitro 실험을 실시하였다. $\gamma$-PGA(PGA-HM, 분자량 300 kDa)를 초음파처리로 저분자화시킨 30 kDa 이하의 저분자 PGA-LM를 만들고, 고분자 PGA-HM과 PGA-LM을 사용하여 실험하였는데 동일한 결과를 얻어 PGA-LM 실험결과 중심으로 보고한 것이다. 아토피 피부발진 NC/Nga 생쥐의 비장에서 B 세포와 T세포를 순수 분리하여 항알레르기 작용에 대한 in vitro 실험을 실시하였다. PGA-LM은 hFCs에 대한 세포독성 실험에서 모든 농도에서 세포독성을 나타내지 않았다. PGA-LM이 B 세포 분화 및 활성화에 미치는 영향을 관찰하기 위하여, NC/Nga 생쥐의 비장에서 순수 분리한 B 세포에 anti-CD40/rmIL-4로 자극한 결과, 대조군은 전사인자인 NF-${\kappa}B$의 활성화로 IL-$1\beta$, IL-6, 그리고 TNF-$\alpha$ mRNA의 발현이 증가되었다. 그러나 PGA-LM과 양성대조군인 rmIL-10 투여군은 염증사이토카인 IL-$1\beta$, IL-6 그리고 TNF-$\alpha$ mRNA 유전자 발현이 감소하였고, IL-10 mRNA 유전자 발현은 증가하였으나 TGF-$\beta$ mRNA의 유전자 발현은 대조군과 큰 차이가 나타나질 않았다. 또한 CD4+ T 세포에 PGA-LM $100\;{\mu}g/ml$를 처리한 후 4일간 동시 배양하여 CD4+IFN-$\gamma$+와 CD4+CD25+foxp3+ Treg 세포를 세포내 염색으로 분석한 결과에서는 CD4+IFN-$\gamma$+인 Th1 세포의 증가와 CD4+CD25+foxp3+ Treg 세포를 증가시켜 알레르기반응에서 우위한 Th2 세포에서 Th1 세포로 전환시키는 면역조절 역할을 나타내었다. 이상의 결과로 NC/Nga 생쥐에서 PGA-LM은 염증유전자 발현을 억제시키고 IFN-$\gamma$+의 증가 및 조절 T 세포의 유도로 아토피피부염의 피부발진을 치료하는 면역조절제로 사용될 수 있을 것으로 생각된다.

• 동의생리병리학회지
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• 제22권4호
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• pp.856-862
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• 2008

The purpose of this study was to evaluate the effect of Samsoeum(SSE) on cytokine regulation of mouse T cells. The proliferation of mouse CD4 T cells under the influence of SSE extract was measured. When mouse CD4 T cell were stimulated with anti-CD3 and anti-CD28 in various concentrations of SSE extract, it increased proliferation of CD4 cells by 30% in $50{\mu}g/m{\ell}$ concentration. The proliferation of CD4 cells increased in $100{\mu}g/m{\ell}$ and $200{\mu}g/m{\ell}$. Treatment of CD4+ T cells stimulated by anti-CD3e and anti-CD28 with SSE resulted in reduction of $IFN-{\gamma}$ and IL-4 levels. SSE has dose-dependent inhibitory effect on $IFN-{\gamma}$ and decreased IL-4 by 70% at 50, $200{\mu}g/m{\ell}$. Oral administration of SSE resulted in increase of CD8+ T cell population in Balb/c mice by 8%. CD4+ T cells under Th1/Th2 polarizing conditions for 3 days with SSE resulted in decrease of $IFN-{\gamma}$ level in Th1 cells by 44% and increase of IL-4 level in Th2 cells by 60%. Experimental results of this study show that SSE induces mouse T-cell to transform into Th2, and increases T-cell population and activation.

• Tuberculosis and Respiratory Diseases
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• 제59권3호
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• pp.272-278
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• 2005

배 경 : 결핵의 보호면역 반응에서 CD8+T 세포에 의한 여러 기전이 중요한 역할을 한다는 사실이 최근에 보고되고 있다. $IFN-{\gamma}$ 분비 외에도 결핵균으로 감염된 세포에 독성을 나타내어 직접 결핵균으로 감염된 세포를 제거하는 독성능 또한 그 역할이 중요하다고 알려지고 있는데, BCG 예방접종을 받은 개체에서도 이러한 균체항원에 특정한 CD8+T 세포의 독성능이 유도되어 있어서 보호면역 반응에서의 역할을 하는지 연구하였다. 대상 및 방법 : HLA-A*0201 과 A*0206를 표현하며 BCG 예방접종을 한 개체들의 혈액에서 백혈구를 분리하고 균체항원의 항원결정기 ($ThyA_{30-38}$) 에 대한 독성능과 ex vivo $IFN-{\gamma}$ 분비능을 유도하였다. 결 과 : 이들 대상에게서 $IFN-{\gamma}$ 분비능과 독성능이 유도되는 것을 관찰할 수 있었고, 또한 HLA-A*0201에 결합하여 CD8+T 세포의 면역 반응을 일으키는 $ThyA_{30-38}$ 펩티드들은 HLA-A*0206인 개체에서도 면역반응을 일으키는 것을 관찰할 수 있었다. 결 론 : 균체 항원에 특정한 CD8+T 세포들의 $IFN-{\gamma}$ 분비 능과 독성능이 BCG 백신주사를 맞은 개체에서 유도되어 있는 것을 관찰할 수 있었다. 따라서 이러한 균체항원에 특정한 CD8+T 세포들이 보호면역 반응에 관여한다는 것을 제시하며, 또한 HLA-A*0201 개체들과 HLA-A*0206 개체들을 대상으로 하는 백신이나 치료제로써 $ThyA_{30-38}$ 펩티드의 사용 가능성을 제시한다.

• Parasites, Hosts and Diseases
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• 제54권2호
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• pp.163-171
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• 2016

As most infections by the helminth parasite elicit the recruitment of $CD4^+CD25^+Foxp3^+$ T ($T_{reg}$) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated $T_{reg}$ cells, we compared the expression levels of $T_{reg}$ cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of $T_{reg}$ cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated $T_{reg}$ cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of $T_{reg}$ cells in the muscle tissue.