• 제목/요약/키워드: Effector Functions

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The Emerging Role of Natural Killer Cells in Innate and Adaptive Immunity

  • Kim, Eun-Mi;Ko, Chang-Bo;Myung, Pyung-Keun;Cho, Daeho;Choi, Inpyo;Kang, Hyung-Sik
    • IMMUNE NETWORK
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    • 제4권4호
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    • pp.205-215
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    • 2004
  • In the early host defense system, effector function of natural killer (NK) cells results in natural killing against target cells such as microbe-infected, malignant, and certain allogenic cells without prior stimulation. NK cell cytotoxicity is selectively regulated by homeostatic prevalence between a repertoire of both activating and inhibitory receptors, and the discrimination of untransformed cells is achieved by recognition of major histocompatibility complex (MHC) class I alleles through inhibitory signals. Although it is well known that the bipotential T/NK progenitors are derived from the common precusor, functional mechanisms in terms of the development of NK cells remain to be further investigated. NK cells are mainly involved in innate immunity, but recent studies have been reported that they also play a critical role in adaptive immune responses through interaction with dendritic cells (DC). This interaction will provide effector functions and development of NK cells, and elucidation of its precise mechanism may lead to therapeutic strategies for effective treatment of several immune diseases.

Induction of Intersex and Masculinization of the Equilateral Venus, Gomphina veneriformis (Bivalvia: Veneridae) by Zinc

  • Ju, Sun-Mi;Park, Jung-Jun;Lee, Jung-Sick
    • Animal cells and systems
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    • 제13권3호
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    • pp.339-344
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    • 2009
  • This study aims to find out the effect of heavy metals, as is the case of EDCs (endocrine disrupting chemicals), on reproductive endocrine disruption of aquatic animals. In the present experiment zinc, which is a heavy metal well known for its androgenous activity, was used. The experimental period was 24 weeks, starting in November during the inactive stage of the clam's reproductive cycle. The experimental groups were composed of one control condition and three zinc exposure conditions (0.64, 1.07, and 1.79 mg/L). The sex ratio (F:M) was 1:1.06 in the control group and 1:1.70 in all the exposed group, illustrating the tendency for higher proportion of males with increases in zinc concentration. Gonad maturity was higher in 1.07, and 1.79 mg/L groups compared to the control group, with higher maturity observed in males than females. Intersex individuals made up 24.7% of the exposed group, while females exhibited a higher ratio than the males with increasing zinc concentration. The results of this study indicate that zinc functions as an androgenic effector on the reproduction of Gomphina veneriformis.

Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, and Inflammation

  • Kim, Chang H.;Park, Jeongho;Kim, Myunghoo
    • IMMUNE NETWORK
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    • 제14권6호
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    • pp.277-288
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    • 2014
  • T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We review the current status of our understanding of SCFA functions in regulation of peripheral T cell activity and discuss their impact on tissue inflammation.

영지버섯 다당체의 항미생물작용 및 항암작용에 관한 연구 (Studies on Anti-Mcirobial and Anti-Cancer Functions of Polysaccharide Extracted from Ganoderma lucidum)

  • 김성환
    • 한국식품영양과학회지
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    • 제27권6호
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    • pp.1183-1188
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    • 1998
  • This study was carried out to elucidate the immunomodulating activity of protein bound polysac charide extracted from Ganoderma lucidum(PSG). Macrophage drived reactive radicals were known as an effector for antimicrobial and anticancer functions. The promising immune response molecule, reactive oxygen intermediates(ROIs), was determined in TIB 71 cells with PSG at various experimental conditions. Treatment with 0.5mg PSG significantly increased the production of ROIs, superoxide anion as well as hydrogen peroxide, from TIB 71 cells(p<0.001). Under the same concentration, con siderable results were obtained from 24 hour cultivation with 106 cells at 5% CO2 incubator. The cells were trigged with PMA(5.3 M) after primed BCG(100 M) or IFN (100U) alone could not induce the production of ROIs, but it had a significant potentiating effect on ROIs secretion when the cells were treated with PSG.

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The complex role of extracellular vesicles in HIV infection

  • Jung-Hyun Lee
    • BMB Reports
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    • 제56권6호
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    • pp.335-340
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    • 2023
  • During normal physiological and abnormal pathophysiological conditions, all cells release membrane vesicles, termed extracellular vesicles (EVs). Growing evidence has revealed that EVs act as important messengers in intercellular communication. EVs play emerging roles in cellular responses and the modulation of immune responses during virus infection. EVs contribute to triggering antiviral responses to restrict virus infection and replication. Conversely, the role of EVs in the facilitation of virus spread and pathogenesis has been widely documented. Depending on the cell of origin, EVs carry effector functions from one cell to the other by horizontal transfer of their bioactive cargoes, including DNA, RNA, proteins, lipids, and metabolites. The diverse constituents of EVs can reflect the altered states of cells or tissues during virus infection, thereby offering a diagnostic readout. The exchanges of cellular and/or viral components by EVs can inform the therapeutic potential of EVs for infectious diseases. This review discusses recent advances of EVs to explore the complex roles of EVs during virus infection and their therapeutic potential, focusing on HIV-1.

IL-15 in T-Cell Responses and Immunopathogenesis

  • Hoyoung Lee;Su-Hyung Park;Eui-Cheol Shin
    • IMMUNE NETWORK
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    • 제24권1호
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    • pp.11.1-11.18
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    • 2024
  • IL-15 belongs to the common gamma chain cytokine family and has pleiotropic immunological functions. IL-15 is a homeostatic cytokine essential for the development and maintenance of NK cells and memory CD8+ T cells. In addition, IL-15 plays a critical role in the activation, effector functions, tissue residency, and senescence of CD8+ T cells. IL-15 also activates virtual memory T cells, mucosal-associated invariant T cells and γδ T cells. Recently, IL-15 has been highlighted as a major trigger of TCR-independent activation of T cells. This mechanism is involved in T cell-mediated immunopathogenesis in diverse diseases, including viral infections and chronic inflammatory diseases. Deeper understanding of IL-15-mediated T-cell responses and their underlying mechanisms could optimize therapeutic strategies to ameliorate host injury by T cell-mediated immunopathogenesis. This review highlights recent advancements in comprehending the role of IL-15 in relation to T cell responses and immunopathogenesis under various host conditions.

Molecular determinants of the host specificity by Xanthomonas spp.

  • Heu, Sunggi;Choi, Min-Seon;Park, Hyoung-Joon;Lee, Seung-Don;Ra, Dong-Soo
    • 한국식물병리학회:학술대회논문집
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    • 한국식물병리학회 2004년도 The 2004 KSPP Annual Meeting & International Symposium
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    • pp.65-67
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    • 2004
  • During initial interactions of bacteria with their host plants, most plants recognize the bacterial infections and repel the pathogen by plant defense mechanism. The most active plant defense mechanism is the hypersensitive response (HR) which is the localized induced cell death in the plant at the site of infection by a pathogen. A primary locus induced in gram-negative phytopathogenic bacteria during this initial interaction is the Hrp locus. The Hrp locus is composed of a cluster of genes that encodes the bacteral Type 111 machinery that is involved in the secretion and translocation of effector proteins to the plant cell. DNA sequence analysis of hrp gene in phytopathogenic bacteria has revealed a Hrp pathogenicity is]and (PAI) with a tripartite mosaic structure. For many gram-negative pathogenic bacteria, colonization of the host's tissue depends on the type III protein secretion system (TTSS) which secrets and translocates effector proteins into the host cell. Effectors can be divided into several groups including broad host range effectors, host specific effectors, disease specific effectors, and effectors inhibit host defenses. The role of effectors carrying LRR domain in plant resistance is very elusive since most known plant resistance gene carry LRR domain. Host specific effectors such as several avr gene products are involved in the determination of the host specificity. Almost all the phytopathogenic Xanthomonas spp. carry avrBs1, avrBs2, and avrBs3 homologs. Some strains of X. oryzae pv. oryzae carry more than 10 copies of avrBs3 homologs. However, the functions of all those avr genes in host specificity are not characterized well.;

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Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy

  • Cho, Jaewon;Tae, Nara;Ahn, Jae-Hee;Chang, Sun-Young;Ko, Hyun-Jeong;Kim, Dae Hee
    • Biomolecules & Therapeutics
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    • 제30권5호
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    • pp.418-426
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    • 2022
  • Chimeric antigen receptor T (CAR-T) cell therapy is one of the promising anticancer treatments. It shows a high overall response rate with complete response to blood cancer. However, there is a limitation to solid tumor treatment. Additionally, this currently approved therapy exhibits side effects such as cytokine release syndrome and neurotoxicity. Alternatively, bispecific antibody is an innovative therapeutic tool that simultaneously engages specific immune cells to disease-related target cells. Since programmed death ligand 1 (PD-L1) is an immune checkpoint molecule highly expressed in some cancer cells, in the current study, we generated αCD3xαPD-L1 bispecific antibody (BiTE) which can engage T cells to PD-L1+ cancer cells. We observed that the BiTE-bound OT-1 T cells effectively killed cancer cells in vitro and in vivo. They substantially increased the recruitment of effector memory CD8+ T cells having CD8+CD44+CD62Llow phenotype in tumor. Interestingly, we also observed that BiTE-bound polyclonal T cells showed highly efficacious tumor killing activity in vivo in comparison with the direct intravenous treatment of bispecific antibody, suggesting that PD-L1-directed migration and engagement of activated T cells might increase cancer cell killing. Additionally, BiTE-bound CAR-T cells which targets human Her-2/neu exhibited enhanced killing effect on Her-2-expressing cancer cells in vivo, suggesting that this could be a novel therapeutic regimen. Collectively, our results suggested that engaging activated T cells with cancer cells using αCD3xαPD-L1 BiTE could be an innovative next generation anticancer therapy which exerts simultaneous inhibitory functions on PD-L1 as well as increasing the infiltration of activated T cells having effector memory phenotype in tumor site.

Increase of Vδ2+ T Cells That Robustly Produce IL-17A in Advanced Abdominal Aortic Aneurysm Tissues

  • In-Ho Seo;Seung-Jun Lee;Tae Wook Noh;Jung-Hwan Kim;Hyun-Chel Joo;Eui-Cheol Shin;Su-Hyung Park;Young-Guk Ko
    • IMMUNE NETWORK
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    • 제21권2호
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    • pp.17.1-17.10
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    • 2021
  • Abdominal aortic aneurysm (AAA) is a chronic dilation of the aorta with a tendency to enlarge and eventually rupture, which constitutes a major cause of cardiovascular mortality. Although T-cell infiltrates have been observed in AAA, the cellular, phenotypic, and functional characteristics of these tissue-infiltrating T cells are not fully understood. Here, we investigated the proportional changes of T-cell subsets-including CD4+ T cells, CD8+ T cells, and γδ T cells-and their effector functions in AAAs. We found that Vδ2+ T cells were presented at a higher frequency in aortic aneurysmal tissue compared to normal aortic tissue and PBMCs from patients with AAA. In contrast, no differences were observed in the frequencies of CD4+, CD8+, and Vδ1+ T cells. Moreover, we observed that the Vδ2+ T cells from AAA tissue displayed immunophenotypes indicative of CCR5+ non-exhausted effector memory cells, with a decreased proportion of CD16+ cells. Finally, we found that these Vδ2+ T cells were the main source of IL-17A in abdominal aortic aneurysmal tissue. In conclusion, our results suggest that increased Vδ2+ T cells that robustly produce IL-17A in aortic aneurysmal tissue may contribute to AAA pathogenesis and progression.

Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity

  • Hye Won Lee;Yun Shin Chung;Tae Jin Kim
    • IMMUNE NETWORK
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    • 제20권1호
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    • pp.5.1-5.15
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    • 2020
  • The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.