• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9945-9948
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• 2014

Background: The purpose of this study was to investigate Tim-3 expression on peripheral CD3-CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells in lung cancer patients. Materials and Methods: We analyzed Tim-3+CD3-CD56+ cells, Tim-3+CD3-$CD56^{dim}$ cells, Tim-3+CD3-$CD56^{bright}$ cells, and Tim-3+CD3+CD56+ cells in fresh peripheral blood from 79 lung cancer cases preoperatively and 53 healthy controls by flow cytometry. Postoperative blood samples were also analyzed from 21 members of the lung cancer patient cohort. Results: It was showed that expression of Tim-3 was significantly increased on CD3-CD56+ cells, CD3-$CD56^{dim}$ cells and CD3+CD56+ cells in lung cancer patients as compared to healthy controls (p=0.03, p=0.03 and p=0.04, respectively). When analyzing Tim-3 expression with cancer progression, results revealed more elevated Tim-3 expression in CD3-CD56+ cells, CD3-$CD56^{dim}$ cells and CD3+CD56+ cells in cases with advanced stages (III/IV) than those with stage I and II (p=0.02, p=0.04 and p=0.01, respectively). In addition, Tim-3 expression was significantly reduced on after surgical resection of the primary tumor (p<0.01). Conclusions: Tim-3 expression in natural killer cells from fresh peripheral blood may provide a useful indicator of disease progression of lung cancer. Furthermore, it was indicated that Tim-3 might be as a therapeutic target.

• Clinical and Experimental Pediatrics
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• 제53권2호
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• pp.136-145
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• 2010

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called $V{\alpha}14J{\alpha}18$ in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, ${\alpha}-galactosylceremide$ (${\alpha}-GalCer$), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and $interferon-{\gamma}$. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with ${\alpha}-GalCer$. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.

• Journal of Periodontal and Implant Science
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• 제23권2호
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• pp.300-314
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• 1993

Periodontal disease research has been focused on understanding the immunopathologic mechanisms which may operate in the development and maintenance of peiodontal inflammatory changes. Immunologic and inflammatory responses may relate to the etiology and pathogenesis of periodontal disease. In order to research immunopathology of periodontal disease, previous investigators have spent much time on the distribution of lymphocyte subpopulations and NK cells but they have spent less time on the changes of those cells to the periodontal disease severity. The purpose of study was performed to investigate the changes of the distribution of T lymphocytes, B lymphocytes, T lymphocyte subsets, and Natural Killer cells in the gingival epithelium and connective tissue of the periodontal disease with the various clinical parameters including Gingival Index, Sulcular Bleeding Index, and pocket depth. Gingival tissues were obtained from 25 patients with different severity of periodontal disease. Serial cryostat sections displaying a cross section of gingiva were labelled with monoclonal antibody for pan T cells, T cytotoxic/suppressor cells, T helper/inducer cells, pan B cells, and NK cells were develped using an avidin-biotin-peroxidase system. Lymphocyte populations were enumerated in repeatable fields from gingival section. 1. T cells were more increased at grade 1 and 3 than at grade 0 of gingival index (p<0.05). Helper T cells and NK cells were significantly increased at grade 1, 2, 3 than at grade 0(p<0.05). 2. T cells were more decreased at grade 3 and 4 than at grade 1 of sulcular bleeding index (p<0.01, p<0.05). Especially, Natural Killer cells were significantly increased at grade 1, 2, 3, 4 than at grade 0 (p<0.05, p<0.001). 3. The ratios of helper T/suppressor T cells were more decreased at grade 4 than at grade 0 and at grade 4 than at grade 2 of sulcular bleeding index (p<0.05, p<0.05). 4. Helper T cells were significantly decreased at grade II and III than at grade I, however the Natural Killer cells showed a increasing tendency with the increase of the pocket depth, there were no significant differences between each grade of pocket depth. 5. The ratios of helper T/suppressor T cells were tended to be decreased with the increase of the pocket depth, there were no significant differences between each grades of pocket depth. There was a very weak change in the distribution of T lymphocytes, B lymphocytes, T lymphocyte subsets, and Natural Killer cells in the gingival epithelium and connective tissue of the periodontal lesion with the various clinical parameters including gingial index, sulcular bleeding index, and pocket depth. But, the number of T lymphocytes and Natural Killer cells were significantly changed in gingival index and sulcular bleeding index.

• Journal of Korean Neurosurgical Society
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• 제66권4호
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• pp.356-381
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• 2023

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the blood-brain-barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versus-host disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

• IMMUNE NETWORK
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• 제13권5호
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• pp.168-176
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• 2013

In the last few years major progress has been made in better understanding the role of natural killer (NK) cells in hepatitis C virus (HCV) infection. This includes multiple pathways by which HCV impairs or limits NK cells activation. Based on current genetic and functional data, a picture is emerging where only a rapid and strong NK cell response early on during infection which results in strong T cell responses and possible subsequent clearance, whereas chronic HCV infection is associated with dysfunctional or biased NK cells phenotypes. The hallmark of this NK cell dysfunction is persistent activation promoting ongoing hepatitis and hepatocyte damage, while being unable to clear HCV due to impaired IFN-${\gamma}$ responses. Furthermore, some data suggests certain chronically activated subsets that are $NKp46^{high}$ may be particularly active against hepatic stellate cells, a key player in hepatic fibrogenesis. Finally, the role of NK cells during HCV therapy, HCV recurrence after liver transplant and hepatocellular carcinoma are discussed.

• 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.

• Molecules and Cells
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• 제37권5호
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• pp.365-371
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• 2014

Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

• 대한의생명과학회지
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• 제2권2호
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• pp.211-222
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• 1996

수태기간중 태아가 모체에 의해 면역학적으로 거부반응을 일으키지 않고 동종이식 상태로 유지되는 기작을 밝히는 연구의 일환으로 C3H/HeJ계의 암컷 생쥐와 DBA/2계의 수컷 생쥐를 교배하여 모체에서 발생되는 체계적인 면역기능 및 국소적 면역기능현상에 대하여 연구하고자 수태기 간별로 비 장 및 자궁으로 들어가는 림프절에서 T세포 및 B세포의 아형을 측정하였고 자연살해 세포의 활성도를 측정하였다. 또한 수태혈청 및 수태성 호르몬이 자연살해세포의 활성도에 미치는 영향을 알아보았다. 각 수태기간별로 비장세포에 있어서 T세포와 B세포의 아형을 관찰한 결과, Thy-1.2$^{+}$세포는 수태기간중 중기 이후에 감소하기 시작하여 수태 4기에는 대조군에 비하여 유의하게 감소하였으며 수태말기에는 회복하였다. L3T4$^{+}$세포도 Thy-1.2$^{+}$ 세포와 비교하여 비슷한 경향으로 감소 또는 증가하였다. Ly2$^{+}$세포는 수태중기 이후부터 대조군에 비하여 유의하게 증가하였으며 B세포는 수태중기 이후부터 수태말기까지 계속 증가하였다. 비장에 있어서 자연살해세포의 세포독성은 수태 5일에서 수태 8일 사이에 가장 증가하였으며 그 이후는 대조군 수준으로 감소하였다. 정상혈청 및 수태혈청의 자연살해세포의 세포독성에 대한 영향을 수태시기별로 조사한 결과, 정상혈청과 수태혈청 모두 자연살해세포의 세포독성을 유의하게 억제하였으며, Progesterone은 시험관내실험과 생체내 실험 모두 약리적인 농도이상에서 농도에 의존적으로 자연살해세포의 세포독성을 증가시켰으며, HCG는 5 unit/ml에서 5000 unit/ml까지 처리농도에 비례하여 자연살해세포의 세포독성을 억제하였다. 자궁으로 들어가는 림프절에서 T세포의 아형은 Thy-1.2$^{+}$세포는 수태 2기부터 증가하여 대조군에 보다 유의하게 증가하였으며, L3T4$^{+}$세포의 유의한 변화없이 Ly2$^{+}$세포가 수태 2기 이후부터 대조군에 비하여 유의하게 증가하였고 분만 직전에는 조금 감소하였다. 자궁으로 들어가는 림프절에서의 자연살해세포의 세포독성은 착상직후 대조군에 비하여 유의하게 증가하였으며, 수태중기와 수태후기에도 대조군에 비하여 세포독성이 증가하였으며, 같은 시기의 비장세포의 자연살해세포의 세포독성보다 높게 나타났다.

• IMMUNE NETWORK
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• 제23권1호
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• pp.8.1-8.13
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• 2023

CD8⁺ T cells are activated by TCRs that recognize specific cognate Ags, while NK-cell activation is regulated by a balance between signals from germline-encoded activating and inhibitory NK receptors. Through these different processes of Ag recognition, CD8⁺ T cells and NK cells play distinct roles as adaptive and innate immune cells, respectively. However, some human CD8⁺ T cells have been found to express activating or inhibitory NK receptors. CD8⁺ T-cell populations expressing NK receptors straddle the innate-adaptive boundary with their innate-like features. Recent breakthrough technical advances in multi-omics analysis have enabled elucidation of the unique immunologic characteristics of these populations. However, studies have not yet fully clarified the heterogeneity and immunological characteristics of each CD8⁺ T-cell population expressing NK receptors. Here we aimed to review the current knowledge of various CD8⁺ T-cell populations expressing NK receptors, and to pave the way for delineating the landscape and identifying the various roles of these T-cell populations.

• 생약학회지
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• 제22권4호
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• pp.233-239
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• 1991

Phellinus linteus was examined for its anticancer activity using an animal model. Water extract of Phellinus linteus was prepared from artificially cultivated mycelia. Neither toxicity nor abnormal changes of hematological parameters were observed in the rat given orally with high doses of drug extract for 15 days. ICR mice were transplanted with Sarcoma-180 tumor cells intraperitoneally and drug extract was daily given to the mice from 1 day after tumer transplantation for 3 weeks. Administration of drug extract significantly prolonged the survival duration of Sarcoma 180-transplanted mice. For the better understanding of the anticancer activity, we have examined the effect of the drug extract administration on various killer cell functions, such as natural killer(NK) cells, cytotoxic T-lymphocytes (CTL) and macrophages which have been known to be main effector cells in immune responses against tumors. The results from the 4 hr $^{51}Cr-release$ assay have shown that the drug extract augments mouse NK cell activity but neither CTL nor macrophages. It is possible, then, that the anticancer activity of the Phellinus linteus may be associated with augmentation of NK cell function in the cancerated hosts.