• 제목/요약/키워드: antigen-presenting cell function

검색결과 40건 처리시간 0.026초

골수성백혈병에서 배양한 수지상세포(Dendritic Cell)에 대한 종양항원 감작법으로 IL-12 첨가와 융합법의 효과 (The Effectiveness of IL-12 Administration and Fusion on Tumor Antigen Sensitization Methods for Dendritic Cells Derived from Patients with Myelogenous Leukemia)

  • 김기원;박석영;홍영선
    • IMMUNE NETWORK
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    • 제4권1호
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    • pp.38-43
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    • 2004
  • Backgroud: Immunotherapy using dendritic cells (DC) loaded with tumor antigens may represent a potentially effective method for inducing antitumor immunity. We evaluated the effectiveness of DC-based antitumor immune response in various conditions. Methods: DC were cultured from peripheral blood mononuclear cells (PBMNC) in myelogenous leukemia (ML) and lysates of autologous leukemic cells are used as tumor antigen. The effectiveness of interleukin-12 (IL-12) and CD40L (CD154) on the antigen presenting function of lysates-loaded DC was analyzed by proliferation, cytokine production, and cytotoxicity tests with activated PBMNC (mainly lymphocytes). For generating antigen-loaded DC, direct fusion of DC with ML was studied. Results: Antigen loaded DC induced significantly effective antitumor immune response against autologous leukemic cells. Administration of IL-12 on the DC based antitumor immune response showed higher proliferation activity, IFN-$\gamma$ production, and cytotoxic activity of PBMNC. Also, fused cell has a potent antitumor immune response. Conclusion: We conclude that lysates-loaded DC with IL-12 may be effectively utilized as inducer of antitumor immune reaction in ML and in vivo application with DC-based antitumor immunotherapy or tumor vaccination seems to be feasible.

($Interferon{\gamma}$)로 자극된 치은섬유아세포와 치주인대섬유아세 포에서 항원제시기능과 관련된 세포 표면분자의 발현 (Expression of Antigen Presenting Function-Associated Surface Molecules on $Interferon{\gamma}$-Treated Gingival Fibroblasts and Periodontal Ligament Fibroblasts)

  • 서석란;류성훈;오귀옥;김형섭
    • Journal of Periodontal and Implant Science
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    • 제30권4호
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    • pp.895-913
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    • 2000
  • It is becoming increasingly clear that human gingival fibroblasts(HGF) may play a role in regulating immune responsiveness in inflammatory periodontal lesions. Stimulation of HGF with locally-secreted T cell cytokine $IFN_{\gamma}$ induces human leukocyte antigen class II(HLA II) expression on HGF, which is one of the characteristic feature of professional antigen presenting cells(pAPC). However, $IFN_{\gamma}$-treated HGF and other nonprofessional antigen presenting cells(npAPC) are known to be ineffective or less effective antigen presenter to resting T cells. This study, therefore, was undertaken in an effort to elucidate the differences in expression of cell surface molecules between npAPC in periodontal tissues, such as HGF and periodontal ligament fibroblasts(PDLF), and pAPC such as monocytes/macrophages. Using flow cytometry, the levels of cell surface expression of HLA-D, ICAM-1, LFA-3, and B7-1, which are involved in antigen presentation, were determined in HGF, PDLF and human myelomonocytic cell line THP-1. $IFN_{\gamma}$ clearly induced HLA-D expression on both of fibroblasts and monocytes dose dependently. However, expression level on monocytes were 4 to 5 times higher than that on fibroblasts, and induction rate was faster in monocytes than in fibroblasts. The levels of ICAM-1 expression on fibroblasts and monocytes were enhanced by $IFN_{\gamma}$ in a dose dependent manner. On the other hand, the expression of LFA-3 molecule, which could be detected in fibroblasts and monocytes without cytokine stimulation, was no more enhanced by addition of $IFN_{\gamma}$. B7-1, important costimulatory molecule in T cell activation and proliferation, was not detected on both of fibroblasts and monocytes even when stimulated with $IFN_{\gamma}$, except on monocytes fully differentiated by pretreatment of PMA and treated by $IFN_{\gamma}$. These results suggest that delayed expression of HLA-D and absence of B7-1 on $IFN_{\gamma}$ - treated fibroblasts may at least in part be involved in the ineffectiveness of fibroblasts as primary APC. And it is postulated that although periodontal fibroblasts may not serve as primary APC in normal periodontium, sustained expression of HLA II on ubiquitous fibroblasts in inflammatory lesions may perpetuate immune responses and produce chronic inflammation and tissue injury.

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Inhibition of Major Histocompatibility Complex (MHC)-Restricted Presentation of Exogenous Antigen in Dendritic Cells by Korean Propolis Components

  • Han, Shin-Ha;Cho, Kyung-Hae;Lee, Seung-Jeong;Lee, Chong-Kil;Song, Young-Cheon;Ha, Nam-Joo;Kim, Kyung-Jae
    • IMMUNE NETWORK
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    • 제5권3호
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    • pp.150-156
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    • 2005
  • Background: Dendritic cells (DCs) playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of antigen presenting cell (APC) function of DCs, we searched for and characterized APC function modulators from natural products. Methods: DCs were cultured in the presence of propolis components, WP and CP, and then examined for their ability to present exogenous antigen in association with major histocompatibility complexes (MHC). Results: WP and CP inhibited class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells, and DCs generated from bone marrow cells with GM-CSF and IL-4. The inhibitory activity of WP and CP appeared to be due not only to inhibition of phagocytic activity of DCs, but also to suppression of expression of MHC molecules on DCs. We also examined the effects of WP and CP on T cells. Interestingly, WP and CP increased IL-2 production from T cells. Conclusion: These results demonstrate that WP and CP inhibit MHC-restricted presentation of exogenous antigen through down-regulation of phagocytic activity and suppression of expression of MHC molecules on DCs.

수지상세포의 CD1b 분자와 포식작용의 증가 (CD1b in immature dendritic cells acquires increased phagocytotic function)

  • 류현정
    • 미생물학회지
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    • 제54권3호
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    • pp.222-227
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    • 2018
  • CD1 분자는 결핵균 유래 지질항원 발현하는 단백질이며, 특히 수지상세포(dendritic cells)가 결핵균 감염시에 발현이 점차 감소함을 관찰하였다. 이는 결핵균의 사균이나 항원만으로는 관찰되지 않는 결과였다. 2차원 전기영동(2D electrophoresis)을 통하여 CD1b 의 인산화를 관찰하였고 이러한 현상이 식세포작용과 연관됨을 확인하였다.

Human $CD103^+$ dendritic cells promote the differentiation of Porphyromonas gingivalis heat shock protein peptide-specific regulatory T cells

  • Kim, Myung-Jin;Jeong, Eui-Kyong;Kwon, Eun-Young;Joo, Ji-Young;Lee, Ju-Youn;Choi, Jeomil
    • 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.

Actin Engine in Immunological Synapse

  • Piragyte, Indre;Jun, Chang-Duk
    • IMMUNE NETWORK
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    • 제12권3호
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    • pp.71-83
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    • 2012
  • T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse.

T cell costimulation by CD28, CTLA-4, and ICOS

  • Lee, Kyung-Mi
    • IMMUNE NETWORK
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    • 제1권2호
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    • pp.95-103
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    • 2001
  • T cells play a central role in the initiation and regulation of the immune response to foreign antigens. Full activation of T cells requires the engagement of T cell receptor complex (TCR) and the binding of a second costimulatory receptor to its ligand expressed on antigen presenting cells (APC). Among the molecules known to provide costimulatory function, CD28 has been the most dominant and potent costimulatory molecule. However, the function of CD28 is becoming more complex due to the recent discovery of its structural homologue, CTLA-4 and ICOS. This review summarizes the biology and physiologic function of each of these receptors, and further focuses on the biochemical mechanism underlying the function of these receptors. Complete understanding of the CD28/CTLA-4/ICOS costimulatory pathway will provide the basis for developing new therapeutic approaches for immunological dieseases.

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Role of natural killer cells for immunotherapy in chronic myeloid leukemia (Review)

  • Hye‑Rim Lee;Kwang‑Hyun Baek
    • Oncology Letters
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    • 제41권5호
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    • pp.2625-2635
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    • 2019
  • The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin-like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells. The association between KIR and HLA is derived from the diversity of KIR/HLA gene profiles present in different individuals, and this determines the cytotoxic effect of NK cells on cancer cells. Chronic myeloid leukemia (CML) is a hematological leukemia characterized by the hyper-proliferation of myeloid cells, with the majority of patients with CML presenting with abnormal immune cells. Tyrosine kinase inhibitors are the present standard therapy for CML, but are associated with numerous adverse side effects. Various studies have proposed CML therapy by immunotherapeutic approaches targeting the immune cells. This review summarizes the contents of NK cells and the association between KIR/HLA and leukemia, especially CML. This is followed by a discussion on the development of NK cell immunotherapy in hematological malignancies and research into strategies to enhance NK cell function for CML treatment.

Enhancement of Antigen Presentation Capability of Dendritic Cells and Activation of Macrophages by the Components of Bifidobacterium pseudocatenulatum SPM 1204

  • HAN Shinha;CHO Kyunghae;LEE Chong-Kil;SONG Youngcheon;PARK So Hee;HA Nam-Joo;KIM Kyungjae
    • Biomolecules & Therapeutics
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    • 제13권3호
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    • pp.174-180
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    • 2005
  • Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

Tumor Cell Clone Expressing the Membrane-bound Form of IL-12p35 Subunit Stimulates Antitumor Immune Responses Dominated by $CD8^+$ T Cells

  • Lim, Hoyong;Do, Seon Ah;Park, Sang Min;Kim, Young Sang
    • IMMUNE NETWORK
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    • 제13권2호
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    • pp.63-69
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    • 2013
  • IL-12 is a secretory heterodimeric cytokine composed of p35 and p40 subunits. IL-12 p35 and p40 subunits are sometimes produced as monomers or homodimers. IL-12 is also produced as a membrane-bound form in some cases. In this study, we hypothesized that the membrane-bound form of IL-12 subunits may function as a costimulatory signal for selective activation of TAA-specific CTL through direct priming without involving antigen presenting cells and helper T cells. MethA fibrosarcoma cells were transfected with expression vectors of membrane-bound form of IL-12p35 (mbIL-12p35) or IL-12p40 subunit (mbIL-12p40) and were selected under G418-containing medium. The tumor cell clones were analyzed for the expression of mbIL-12p35 or p40 subunit and for their stimulatory effects on macrophages. The responsible T-cell subpopulation for antitumor activity of mbIL-12p35 expressing tumor clone was also analyzed in T cell subset-depleted mice. Expression of transfected membranebound form of IL-12 subunits was stable during more than 3 months of in vitro culture, and the chimeric molecules were not released into culture supernatants. Neither the mbIL-12p35-expressing tumor clones nor mbIL-12p40-expressing tumor clones activated macrophages to secrete TNF-${\alpha}$. Growth of mbIL-12p35-expressing tumor clones was more accelerated in the $CD8^+$ T cell-depleted mice than in $CD4^+$ T cell-depleted or normal mice. These results suggest that $CD8^+$ T cells could be responsible for the rejection of mbIL-12p35-expressing tumor clone, which may bypass activation of antigen presenting cells and $CD4^+$ helper T cells.