1.In vitro Stimulation of Tumor - Draining Lymph Node Lymphocytes with the 30 kDa Antigen of Mycobacterium tuberculosis Leads to the Differentiation of Th1 Cells and Cytotoxic Effector Cells.
Jeong Kyu PARK ; Tae Hyun PAIK ; Seok Shin KOH ; Hwa Jung KIM ; Eun Kyeong JO
Korean Journal of Immunology 1997;19(1):59-72
Tumor-draining lymph node (TDLN) lymphocytes contain immunologically sensitized to tumor but functionally deficient T cells. The 30 kDa protein antigen, a major secreted protein antigen of Mycobacterium tuberculosis, exhibits strong T cell stimulatory effect. In this study, it examined that the feasibility of using M tuberculosis 30 kDa antigen to stimulate tumor-draining lymph node cells for the generation of specific immune effector cells. Freshly isolated TDLN lymphocytes could directly respond to the 30 kDa antigen alone and their proliferative responses were markedly augmented by stimulation with rIL-2. TDLN cells were stimulated with the 30 kDa antigen for various time intervals and examined for the induction of IFN-r and IL-4 mRNA using RT-PCR. The expression of IFN-r mRNA was greatly augmented after 1 wk, whereas IL-4 mRNA is markedly decreased after 1 wk. Cytotoxic T cell activities induced by the 30 kDa antigen was also evaluated. TDLN cells stimulated with the 30 kDa antigen alone were able to generate remarkable cytotoxic response to K562 or Daudi cell lines after 6 days of culture. And their cytotoxic effects were highly augmented by stirnulation with rIL-2. These results suggest that the 30 kDa antigen of M. tuberculosis may selectively activate Thl cells of TDLN lymhocytes and induce the cytotoxic T cell activities. In conclusion, the 30 kDa antigen can be used as a biologic response modifier in tumor immunology.
Allergy and Immunology
;
Cell Line
;
Interleukin-4
;
Lymph Nodes*
;
Lymphocytes*
;
Mycobacterium tuberculosis*
;
Mycobacterium*
;
RNA, Messenger
;
T-Lymphocytes
;
Th1 Cells*
;
Tuberculosis
2.Determination of Anti-tuberculous Antibody Against Triton X-100 Solubilized Protein ( TSP ) Antigen of Mycobacterium tuberculosis in the Sera of Patients with Pulmonary Tuberculosis.
Tae Hyun PAIK ; Jeong Kyu PARK ; Hwa Jung KIM ; Kyung Jin KIM ; Eun Kyeong JO
Journal of the Korean Society for Microbiology 1997;32(1):59-70
Some of the proteins of mycobacteria are preferentially associated with the cell wall and are powerful immunogens, and humoral antibody responses to these mycobacterial antigens may occur in patients with tuberculosis. In this study, Triton X-100 solubilized protein (TSP) antigen was isolated from Mycobacterium tuberculosis H37Rv by overnight shaking with 1% Triton X- 100/PMSF and 10-90% ammonium sulfate precipitation. IgG and IgM antibody levels against TSP, crude protein from the unheated cultrue filtrate (CF#) and 30 kDa antigens were determined in the sera of 80 patients with pulmonary tuberculosis and 99 healthy controls with PPD (+) and (-). High IgG reactivity to TSP and CF antigen was observed in tuberculosis patients. Mean IgG antibody titers against all of three mycobacterial antigens were differed significantly (P<0.01) between patients and controls but IgM showed no difference. By the cut-off value adding 2 standard deviation to the mean absorbance of controls, the sensitivity and specificity of the IgG antibody to TSP antigen were 93.9% and 77.5%. The specificity to TSP antigen was a litttle higher than those obtained by CF and 30 kDa antigen. From the above results, the TSP antigen may be useful for the serodiagnosis of tuberculosis.
Ammonium Sulfate
;
Antibody Formation
;
Cell Wall
;
Humans
;
Immunoglobulin G
;
Immunoglobulin M
;
Mycobacterium tuberculosis*
;
Mycobacterium*
;
Neptune*
;
Octoxynol*
;
Sensitivity and Specificity
;
Serologic Tests
;
Tuberculosis
;
Tuberculosis, Pulmonary*
3.The Enhancing IL-2R alpha mRNA Expression induces A Marked T Cel Proliferation with Interleukin-2 and Anti-CD3 mAb.
Hwa Jung KIM ; Eun Kyeong JO ; Jeong Kyu PARK ; Jong Kun KIM
Korean Journal of Immunology 1998;20(4):427-434
Culture of human peripheral T lymphocytes with irnmobilized anti-CD3 rnAb plus IL-2 resulted in a marked proliferation and the enhancing IL-2Ra mRNA expression. The process of the T cell activation involves a series of biochemical events which ultimately lead to the proliferation and IL-2Ra mRNA expression. Although the above results have been observed, the celluar signal mechanisms between the proliferative response and the IL-2Ra mRNA expression through T cell receptor and IL-2 receptor remains unresolved. In the present study, We have used genistein (the selective PTK inhibitor) or chronic PMA treatment (depletion of intracelluar PKC activity), to investigate the role of PTK or PKC both in a synergistic proliferation and in the enhancing IL-2Ra mRNA expression by IL-2/anti-CD3. Genistein (30 ug/ml) completely blocked IL-2 induced T cell proliferation, and inhibited anti-CD3 induced T cell proliferation (93.4%). But genistein downregulated the IL-2Ra mRNA expression by IL-2, anti-CD3 and IL-2/anti-CD3. The chronic PMA treatment failed to inhibit the proliferation and the IL-2R#u mRNA expression by IL-2 alone. But PKC depleted T cells stimulated with anti-CD3 mAb showed the decrease of the proliferation (68.6%) and IL-2Ra mRNA expression. In activated with IL-2/anti- CD3, the proliferative response showed a half of reduction, but the IL-2Ra mRNA expression were not regulated. These results demonstrate that proliferative response to IL-2 appears to be dependent on PTKs activity and independent of PKC involvement, but the IL-2Ra mRNA expression may be required another signals. PTKs and PKC activity may be important in TCR/CD3 signaling. But IL-2/anti-CD3 are coupled up different signal transduction pathways responsible for the synergistic T cell proliferation and the enhancing IL-2Ru mRNA expression.
Cell Proliferation
;
Genistein
;
Humans
;
Interleukin-2*
;
Receptors, Antigen, T-Cell
;
Receptors, Interleukin-2
;
RNA, Messenger*
;
Signal Transduction
;
T-Lymphocytes
4.A Case of Hypertension Secondary to Paraganglioma of the Posterior Mediastinum..
Eui Kyeong HWANG ; Jae Woong CHOI ; In Hu HWANG ; Chan Hee MUN ; Hyun Jo MIN ; Chang Sup SONG ; Choong Hun SUH ; Eun Ju KO ; Eun Kyeong KIM
Korean Circulation Journal 1997;27(8):895-899
Functional paraganglioma of the mediastinum is an uncommon tumor of the paraganglion system that causes symptoms and signs of episodic catecholamine release. It has not been reported in Korea. We experienced a case of a 17 years old man with a history of diaphoresis and paroxysmal hypertension refractory to therapy since 14 years old. Urinary execretion of catecholamine and its metabolites were elevated. Computed tomography(CT) scan revealed high density mass located on the posterior mediastinum in the area of the right fifth intercostal space. At thoracotomy, a 3X3X4cm sized lesion was resected and confirmed as a paraganglioma.
Adolescent
;
Humans
;
Hypertension*
;
Korea
;
Mediastinum*
;
Paraganglioma*
;
Pheochromocytoma
;
Thoracotomy
5.Host-Pathogen Interactions Operative during Mycobacteroides abscessus Infection
Eun-Jin PARK ; Prashanta SILWAL ; Eun-Kyeong JO
Immune Network 2021;21(6):e40-
Mycobacteroides abscessus (previously Mycobacteroides abscessus; Mabc), one of rapidly growing nontuberculous mycobacteria (NTM), is an important pathogen of NTM pulmonary diseases (NTM-PDs) in both immunocompetent and immunocompromised individuals. Mabc infection is chronic and often challenging to treat due to drug resistance, motivating the development of new therapeutics. Despite this, there is a lack of understanding of the relationship between Mabc and the immune system. This review highlights recent progress in the molecular architecture of Mabc and host interactions. We discuss several microbial components that take advantage of host immune defenses, host defense pathways that can overcome Mabc pathogenesis, and how host-pathogen interactions determine the outcomes of Mabc infection. Understanding the molecular mechanisms underlying host-pathogen interactions during Mabc infection will enable the identification of biomarkers and/or drugs to control immune pathogenesis and protect against NTM infection.
6.Toll-like Receptors and NOD-like Receptors in Innate Immune Defense during Pathogenic Infection.
Hyo Sun JIN ; Jeong Kyu PARK ; Eun Kyeong JO
Journal of Bacteriology and Virology 2014;44(3):215-225
In response to invading pathogens, the body immune system develops an immediate defense mechanism, i.e., innate immune response, which is detected in almost all living organisms including mammals, plants, insects, etc. Recent studies have identified numerous innate immune receptors that are able to recognize pathogen-associated molecular patterns and transduce the essential intracellular signaling cascades to mount early and successful host defenses against infectious challenge. Among innate immune receptors, we will focus on two important receptors, toll-like receptors (TLRs) and nucleotide binding oligomerization domain (Nod)-like receptors, and their major intracellular signaling pathways that culminate to activate innate immune effectors and inflammatory mediators during pathogen infection. In this review, we address the recent advances of understanding intracellular signaling mechanisms by which TLRs and NLRs activate host immune defense and inflammation. The role and regulatory mechanisms by which a subet of NLRs-associated inflammasome activation induce interleukin-1beta secretion and their relevance with host defense will be also discussed. Both TLR- and NLR-mediated intracellular signaling networks serve crucial roles in mounting resistance to bacterial and viral infection through synthesis of immune mediators and antimicrobial chemicals during infection.
Immune System
;
Immunity, Innate
;
Inflammation
;
Insects
;
Interleukin-1beta
;
Mammals
;
Toll-Like Receptors*
7.Macrophage Activation after In vitro Stimulation with the TSP Antigen of Mycobacterium tuberculosis H37Rv.
Seong Kyu PARK ; Eun Kyeong JO ; Jae Hyun LIM ; Hwa Jung KIM ; Jeong Kyu PARK ; Tae Hyun PAIK
Korean Journal of Immunology 1998;20(2):141-151
Present study aimed to investigate the immunological activities of cell wall associated protein antigen solubilized with Triton X-100 (TSP) from Mycobacterium tuberculosis H37Rv and conducted on 43 patients with pulmonary tuberculosis (newly diagnosed, medicated within 12 months and chronic refractory patients) and 17 normal healthy controls. These immunological responses were compared with those induced by the PPD or 30 kDa antigen from M, tuberculosis H37Rv culture filtrates, identified as biologically important secreted proteins. Proliferative responses to mycobacterial antigens were compared in peripheral blood mononuclear cells (PBMC) of healthy subjects and pulmonary tuberculosis patients. Signiticant blastogenic responses to the TSP were observed in healthy tuberculin reactors, newly diagnosed and some of antituberculosis drug-medicated patients by H-thymidine incorporation assay. IL-12 p40 and IFN-r mRNA expressions to the TSP were markedly increased, whereas IL-10 and TNF-a mRNA expressions were decreased at a 5 day-stimulation by PBMC in healthy tuberculin reactors, newly diagnosed and medicated patients. However, patients with chronic refractory tuberculosis exhibited more depressed IL-12 p40 and IFN-r mRNA expressions to all of the antigens than another groups. Interestingly, very low IL-10 and TNF-a mRNA expressions cultured with the TSP were also shown. These data suggest that the TSP may be involved in the macrophage activation by induction of Th1 stimulatory signals, such as IL-12, and suppression of Th1 inhibitory cytokine, IL-10.
Tumor Necrosis Factor-alpha
8.Toll-like Receptors and Innate Immunity.
Journal of Bacteriology and Virology 2011;41(4):225-235
Toll-like receptors (TLRs) are the best-characterized membrane-bound receptors in innate immune cells, including macrophages and dendritic cells. Upon recognition of specific ligands originating from pathogen- and modified self-derived molecules, TLRs trigger intracellular signaling cascades that involve various adaptor proteins and enzymes, resulting in the generation of proinflammatory and antimicrobial responses through the activation of transcription factors such as nuclear factor-kappaB. TLR-dependent signaling pathways are tightly regulated during innate immune responses by a variety of negative regulators. This review focuses on the newly described regulation of TLR-dependent signaling pathways, and emphasizes the roles of TLRs in innate immunity. Efforts to modulate these regulatory pathways and signaling molecules may result in the development of new therapeutic strategies through TLR-based therapy.
Dendritic Cells
;
Immunity, Innate
;
Ligands
;
Macrophages
;
Proteins
;
Toll-Like Receptors
;
Transcription Factors
9.Small Heterodimer Partner and Innate Immune Regulation.
Jae Min YUK ; Hyo Sun JIN ; Eun Kyeong JO
Endocrinology and Metabolism 2016;31(1):17-24
The nuclear receptor superfamily consists of the steroid and non-steroid hormone receptors and the orphan nuclear receptors. Small heterodimer partner (SHP) is an orphan family nuclear receptor that plays an essential role in the regulation of glucose and cholesterol metabolism. Recent studies reported a previously unidentified role for SHP in the regulation of innate immunity and inflammation. The innate immune system has a critical function in the initial response against a variety of microbial and danger signals. Activation of the innate immune response results in the induction of inflammatory cytokines and chemokines to promote anti-microbial effects. An excessive or uncontrolled inflammatory response is potentially harmful to the host, and can cause tissue damage or pathological threat. Therefore, the innate immune response should be tightly regulated to enhance host defense while preventing unwanted immune pathologic responses. In this review, we discuss recent studies showing that SHP is involved in the negative regulation of toll-like receptor-induced and NLRP3 (NACHT, LRR and PYD domains-containing protein 3)-mediated inflammatory responses in innate immune cells. Understanding the function of SHP in innate immune cells will allow us to prevent or modulate acute and chronic inflammation processes in cases where dysregulated innate immune activation results in damage to normal tissues.
Chemokines
;
Child
;
Child, Orphaned
;
Cholesterol
;
Cytokines
;
Glucose
;
Humans
;
Immune System
;
Immunity, Innate
;
Inflammasomes
;
Inflammation
;
Metabolism
;
Orphan Nuclear Receptors
;
Social Control, Formal
;
Toll-Like Receptors
10.Cytokine mRNA Expression in Mononuclear Cells from Lymph Nodes of Tuberculous Lymphadenitis Patients after In Vitro Stimulation with the TSP Antigen of Mycobacterium tuberculosis H37Rv.
Tae Hyun PAIK ; Jeong Kyu PARK ; Hwa Jung KIM ; Eun Kyeong JO ; In Hye CHO ; Jae Hyun LIM
Journal of the Korean Society for Microbiology 1998;33(1):15-26
We isolated Triton X-100 solubilized protein (TSP) antigen which may be preferentially associated with the cell wall of M. tuberculosis. In this study, the proliferative activities and cytokine mRNA expression patterns of the TSP antigen were investigated in peripheral blood mononuclear cells (PBMCs) and lymph node mononuclear cells (LNMCs) from 4 patients with tuberculous lymphadenitis. The results of the TSP antigen were compared with those of the PPD antigen, known as a major seretory protein antigen of M. tuberculosis. The peak proliferative response to the TSP by PBMCs was observed at 0.1 ug/ml, whereas that of LNMCs was at 1.0 ug/ml. All of the patients showed greater blastogenic responses for the PPD than those for the TSP. IFN-r, IL-2, and IL-2Ru mRNA production from PBMCs after stimulation with the TSP were greatly augmented after 48 hrs, whereas IL-4 and IL-10 mRNA were gradually suppressed. In addition, high levels of IL-12 p40 mRNA were detected by PBMCs to the TSP antigen at 3 hrs. Elevated IFN-r and IL-2 mRNA production were observed in freshly isolated LNMCs, whereas IL-4 mRNA production was undetectable in either freshly isolated or mycobacterial antigen-stimulated LNMCs. Furthermore, IL-10 mRNA expression from LNMCs was markedly increased by the PPD antigen, but it was considerably reduced by the TSP antigen after 18 hrs. These data suggest that the TSP antigen may be a strong inducer of cytokine mRNA such as IFN-r, IL-2, and IL-12 which are involved in Thl cell and macrophage activation, and inhibit IL-10 mRNA production in LNMCs. In conclusion, the TSP antigen can be used as a preferential Thl cell immunogen in tuberculous lymphadenitis.
Cell Wall
;
Humans
;
Interleukin-10
;
Interleukin-12
;
Interleukin-2
;
Interleukin-4
;
Lymph Nodes*
;
Macrophage Activation
;
Mycobacterium tuberculosis*
;
Mycobacterium*
;
Octoxynol
;
RNA, Messenger*
;
Tuberculosis
;
Tuberculosis, Lymph Node*