• Title/Summary/Keyword: $CD8^+$ T cell

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Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms

  • Abraham U. Morales-Primo;Ingeborg Becker;Claudia Patricia Pedraza-Zamora;Jaime Zamora-Chimal
    • IMMUNE NETWORK
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    • v.24 no.2
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    • pp.14.1-14.26
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    • 2024
  • The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4+ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8+ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8+ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4+ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

MHC Multimer: A Molecular Toolbox for Immunologists

  • Chang, Jun
    • Molecules and Cells
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    • v.44 no.5
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    • pp.328-334
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    • 2021
  • The advent of the major histocompatibility complex (MHC) multimer technology has led to a breakthrough in the quantification and analysis of antigen-specific T cells. In particular, this technology has dramatically advanced the measurement and analysis of CD8 T cells and is being applied more widely. In addition, the scope of application of MHC multimer technology is gradually expanding to other T cells such as CD4 T cells, natural killer T cells, and mucosal-associated invariant T cells. MHC multimer technology acts by complementing the T-cell receptor-MHC/peptide complex affinity, which is relatively low compared to antigen-antibody affinity, through a multivalent interaction. The application of MHC multimer technology has expanded to include various functions such as quantification and analysis of antigen-specific T cells, cell sorting, depletion, stimulation to replace antigen-presenting cells, and single-cell classification through DNA barcodes. This review aims to provide the latest knowledge of MHC multimer technology, which is constantly evolving, broaden understanding of this technology, and promote its widespread use.

Effects of Curcuma longa L. Extracts on Natural Killer Cells and T Cells (울금 주정 추출물이 자연살해세포와 T 면역세포에 미치는 영향)

  • Ha, Yejin;Kim, Ok-Kyung;Nam, Da-Eun;Kim, Yongjae;Kim, Eun;Jun, Woojin;Lee, Jeongmin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.307-313
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    • 2015
  • The present study investigated the immunomodulatory effects of Curcuma longa L. ethanol extracts on natural killer (NK) cells and T cells. We treated Curcuma longa L. ethanol extracts at concentrations of 20, 50, 100, and $150{\mu}g/mL$ to murine NK cells co-incubated with YAC-1 cells. Curcuma longa L. ethanol extracts resulted in increased NK cell activity compared to the control group at all concentrations. In the groups treated with Curcuma longa L. ethanol extracts, CD69 and IFN-${\gamma}$ expression levels significantly increased compared to the control group at 100 and $150{\mu}g/mL$. In addition, Curcuma longa L. ethanol extracts induced significant elevation of CD8+ T cell numbers in a dose-dependent manner. However, Curcuma longa L. ethanol extracts also led to reduction of CD4+ T cell and MHCII numbers. The findings of this study suggest that Curcuma longa L. ethanol extracts could enhance the immune response through activation of NK and cytotoxic T cells due to a proliferative shift of antigen presentation from MHCII to MHCI, presumably.

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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    • v.21 no.2
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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.

Construction, and In Vitro and In Vivo Analyses of Tetravalent Immunoadhesins

  • Cho, Hoonsik;Chung, Yong-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.22 no.8
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    • pp.1066-1076
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    • 2012
  • Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.

T-cell epitope specificity for Porphyromonas gingivalis heat shock protein in periodontitis (치주염환자의 Porphyromonas gingivalis 열충격단백에 대한 T-세포 항원 결정부위 특이성 연구)

  • Lee, Ji-Young;Lee, Ju-Yeon;Choi, Jeom-Il
    • Journal of Periodontal and Implant Science
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    • v.33 no.4
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    • pp.543-553
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    • 2003
  • Due to considerably high degree of sequence homology between bacterial and human heat shock proteins(hsp), it has been widely thought that this protein might be involved in autoimmune disease mechanisms in humans. To elucidate how stress proteins contribute in the immunopathogenesis of periodontitis, the present study was performed to evaluate the T cell immune responses specific to Porphyromonas gingivalis (P. gingivalis) heat shock protein (hsp)60 and T-cell epitope specificities for P. gingivalis hsp60 in periodontitis. Anti-P. gingivalis IgG antibody titers were elevated in all patients. We could establish P. gingivalis hsp-specific T cell ines from the peripheral blood of peridontitis, a mixture of $CD4^+$ and $CD8^+$ cells. Of 108 overlapping synthetic peptides spanning whole P. gingivalis hsp60 moleculc, ten peptides with cpitopes specifities for T-cell were showed. Interestingly, ten epitopes were also identified as T-cell epitopes in the present study as well as B-cell epitopes in peridontitis. Therefore, all the ten representative epitopes were designated as common T-and B-cell epitopes for peridontitis. It is critical in developing a peptide vaccine strategy for potential prevention of periodontitis. It was concluded that P. gingivalis hsp60 might be involved in the immunoregulatory process of periodontitis with heat shock protein specificities.

T Regulatory Cell Responses to Immunization with a Soluble Egg Antigen in $Schistosoma$ $mansoni$-Infected Mice

  • El-Ahwany, Eman;Bauiomy, Ibrahim Rabia;Nagy, Faten;Zalat, Rabab;Mahmoud, Ola;Zada, Suher
    • Parasites, Hosts and Diseases
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    • v.50 no.1
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    • pp.29-35
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    • 2012
  • The aim of the study is to characterize the phenotypes of $CD4^+$ $CD25^+$ T regulatory cells within the liver granulomas and association with both Foxp-3 gene expression and splenic cytokines. Naive C57BL/6 mice were intravenously injected with multiple doses of the soluble egg antigen (SEA) 7 days before cercarial infection. The immunized and infected control groups were sacrificed 8 and 16 weeks post-infection (PI). Histopathology, parasitological parameters, splenic phenotypes for T regulatory cells, the FOXP-3 expression in hepatic granuloma using real-time PCR, and the associated splenic cytokines were studied. Histopathological examination of the liver revealed remarkable increase in degenerated ova within hepatic granuloma which decreased in diameter at weeks 8 and 16 PI ($P$<0.01). The percentage of T regulatory cells ($CD4^+$ $CD25^+$) increased significantly ($P$<0.01) in the immunized group compared to the infected control at weeks 8 and 16 PI. The FOXP-3 expression in hepatic granulomas increased from 10 at week 8 to 30 fold at week 16 PI in the infected control group. However, its expression in the immunized group showed an increase from 30 at week 8 to 70 fold at week 16 PI. The splenic cytokine levels of pro-inflammatory cytokines, IFN-${\gamma}$, IL-4, and TNF-${\alpha}$, showed significant decreases ($P$<0.05) compared to the infected control group. In conclusion, the magnitude and phenotype of the egg-induced effects on T helper responses were found to be controlled by a parallel response within the T regulatory population which provides protection in worm parasite-induced immunopathology.

The Differential Staging of Murine Thymic Lymphoma Cell Lines, Scid.adh, R1.1 and EL-4

  • Chae, Jong Seok;Kim, Hae-jung;Park, Weon Seo;Bae, Youngmee;Jung, Kyeong Cheon
    • IMMUNE NETWORK
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    • v.2 no.4
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    • pp.217-222
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    • 2002
  • Background: Scid.adh is a recently developed murine thymic lymphoma cell line, which has been used as in vitro model for the study of double negative stage III thymocytes. In this study, we compared the expression profile of a number of genes and proteins, which are tightly related to T cell development and apoptosis, in thymic lymphoma cell lines, R1.1, EL-4, and Scid.adh for the developmental staging. Methods: We examined the expression of development marker genes and proteins in three lymphoma cell lines by flow cytometry and RT-PCR. In addition, the expression of apoptosis-related molecules including bcl-2, bax and Fas was also investigated. Results: As previously reported, Scid.adh cell line expressed CD8 and CD25 but not TCR ${\alpha}$ chain, while R1.1 cells expressed TCR ${\alpha}$ chain and both CD4 and CD8 transcripts. These suggest that R1.1 might be in double positive stage, and low level of CD44 expression and the absence of CD25 support this suggestion. In contrast, EL-4 cells showed high level of TCR ${\alpha}$ chain transcript, and low-level of CD4 expression, suggesting that EL-4 is in more mature stage than R1.1. Further, this suggestion was supported by the lack of mT-20 in EL-4 cells, which is expressed in the immature thymocytes, and Scid.adh and R1.1 cell lines, but not in the terminally differentiated thymocytes and peripheral T cells. Among the apoptosis-related gene, transcripts of bcl-2 gene were detected in both R1.1 and EL-4 but not in Scid.adh cells, while bax was expressed in all cell lines. Fas expression was the highest in EL-4 cells and low in Scid.adh cell line. Conclusion: R1.1 cell may represent double positive stage, and EL-4 is more differentiated cell line. In addition, Scid.adh and EL-4 cell lines are suspected to be useful for the study of function of bcl-2 family and Fas during the thymocyte development, respectively.

Expression Pattern of T Lymphocyte Regulatory Factors in Unstimulated Whole Saliva of Erosive Oral Lichen Planus and Recurrent Aphthous Stomatitis Patients (미란형 구강편평태선과 재발성 아프타성 구내염 환자들의 비자극성 전타액내 T림프구 조절인자들의 발현 양상)

  • Yoon, Seon-Hack;Ko, Hyun-Mi;Park, Ji-Il;Kim, Jae-Hyung
    • Journal of Oral Medicine and Pain
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    • v.34 no.4
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    • pp.363-369
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    • 2009
  • Erosive oral lichen planus (EOLP) and recurrent aphthous stomatitis (RAS) are T-cell mediated inflammatory immune disorders. It was investigated mRNA expression pattern of several regulatory factors, such as, CD28, CD45, CD152, CD154, CD279, which influence T lymphocyte in unstimulated whole saliva (UWS) of EOLP and RAS patients. It was collected unstimulated whole saliva during 10 minute in EOLP 18 people, RAS patients 12 people, healthy control 8 people. We investigated mRNA expression of T lymphocyte regulatory factors, such as, CD28, CD45, CD152, CD154, CD279, with real time reverse transcription polymerase chain reaction. In EOLP group, CD45, CD279 expressed higher and CD154 expressed lower than control. In RAS, CD45, CD270 expressed higher and CD28, CD154 expressed lower than control. In addition CD152 salivary mRNA expression of EOLP is higher than that of RAS. The above results were suggested that the mRNA expression of T lymphocyte regulatory factors in unstimulated whole saliva of EOLP and RAS contributes to diagnosis of diseases.

Effects of SPDJTK(SoPungDoJeokTangKami) and Concurrent Administration of AJ (Atopy cream, Jawoongo) Plus SPDJTK on Atopic Dermatitis-like Skin Lesions in NC/Nga Mouse Induced by BMAC (아토피양(樣) 피부염 NC/Nga 생쥐에서 소풍도적탕가미(消風導赤湯加味)와 아토피크림, 자운고(紫雲膏) 및 소풍도적탕가미(消風導赤湯加味)의 병용투여가 피부염에 미치는 영향)

  • Han, Dal-Soo;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.24 no.1
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    • pp.9-35
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    • 2010
  • Objectives The purpose of this study is to investigate the effect of SPDJTK(SoPungDoJeokTangKami) and concurrent administration of AJ(Atopy cream, Jawoongo)+SPDJTK on atopic dermatitis-like skin lesions by using in NC/Nga atopic dermatitis mouse induced by BMAC-induced mice. Methods Clinical skin score, hematology and Serum total IgE and IgG1 of NC/Nga atopic dermatitis mice were evaluated. Moreover, the cytokine level, total cell number, Immunohistochemical staining and Histological features of axillary lymph node(ALN), draining lymph node(DLN), peripheral blood mononuclear cells(PBMCs) and dorsal skin tissue were used in NC/Nga mice. Results Orally administrated SPDJTK with concurrent administration of SPDJTK and AJ decreased the clinical skin score, total cell number of WBC, eosinophils in blood, serum total IgE & IgG1, IL-5, IL-13, IFN-$\gamma$. Also, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, CD3+CD69+, CD3+CCR3+, CCR3+, CD4+CXCR5+ in ALN, absolute cell number of CD3+CCR3+, CCR3+ in DLN, granulocytes in PBMCs, activation cell number of CD3+CD69+, CCR3+, total cell number of CD3+ T cell in dorsal skin tissue were significantly decreased. Furthermore, thickness of epidermis, infiltrated inflammatory immune cell and mast cell in dermis, amount of Eotaxin2 mRNA, CCR3 mRNA in dorsal skin tissue, gene expression of IL-5, IL-13 mRNA in ALN, CD4+ Th cell in dorsal skin tissue and CCR3+ eosinophils in ALN were all significantly decreased. However, total number of DLN, absolute number of CD3e+ T cell and CD19+ B cell, absolute number of CD4+, number of Th cell in DLN and gene expression of foxp3 mRNA were significantly increased significantly. Conclusions Concurrent administration of SPDJTK and AJ on atopic dermatitis in NC/Nga atopic dermatitis mouse was very effective treatment for atopic dermatitis.