Kinetics of IFN-γ and IL-17 Production by CD4 and CD8 T Cells during Acute Graft-versus-Host Disease

주지민,이학모,오근희,이동섭,최은영 대한면역학회 2014 Immune Network Vol.14 No.2

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-γ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 → BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 → BALB.B GVHD model, we showed that the production of IFN-γ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-γ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

Selection of Thymocytes Expressing Transgenic TCR Specific for a Minor Histocompatibility Antigen, H60

주지민,김민범,류수정,김주영,장준,최은영 대한면역학회 2015 Immune Network Vol.15 No.5

Minor histocompatibility antigens are MHC-bound peptides and contribute to the generation of allo-responses after allogeneic transplantation. H60 is a dominant minor H antigen that induces a strong CD8 T-cell response in MHC-matched allogeneic transplantation settings. Here, we report establishment of a TCR transgenic mouse line named J15, wherein T cells express TCRs specific for H60 in complex with H-2Kb, and different fates of the thymocytes expressing J15 TCRs in various thymic antigenic environments. Thymocytes expressing the J15 TCRs were positively selected and differentiated into CD8+ single positive (SP) cells in the thymus of C57BL/6 mice, wherein the cognate antigen H60 is not expressed. However, thymocytes were negatively selected in thymus tissue where H60 was transgenically expressed under the control of the actin promoter, with double-positive stages of cells being deleted. Despite the ability of the H60H peptide (LTFHYRNL) variant to induce cytotoxic activity from H60-specific CTL lines at ∼50% of the activity induced by normal H60 peptides (LTFNYRNL), J15-expressing thymocytes were positively selected in the thymus where the variant H60H was transgenically expressed. These results demonstrate that a single amino-acid change in the H60 epitope peptide influences the fate of thymocytes expressing the cognate TCR.

Skewed Dendritic Cell Differentiation of MyD88-Deficient Donor Bone Marrow Cells, Instead of Massive Expansion as Myeloid-Derived Suppressor Cells, Aggravates GVHD

이영관,주지민,손우정,오세화,민창기,강명수,신동미,최은영 대한면역학회 2018 Immune Network Vol.18 No.6

Graft-versus-host disease (GVHD), a life-threatening complication after bone marrow transplantation (BMT), is induced by activation of alloreactive donor T cells. Our previous study demonstrated that transplantation of myeloid differentiation factor 88 (MyD88)-deficient knockout (KO) bone marrow (BM) resulted in aggravation of GVHD. Here, to understand the cellular mechanism, we performed longitudinal in vivo imaging and flow cytometric analyses followed by transcriptome and functional examination of donor MyD88-KO BM progenies in GVHD hosts, using a major histocompatibility complex-matched but minor histocompatibility antigen-mismatched C57BL/6→BALB.B model. In GVHD hosts with MyD88-KO BMT, donor BM-derived CD11b+Gr-1+ cells were found to undergo cell death, a fate significantly different from the explosive expansion shown by the wild type (WT) counterparts, and also from the moderate expansion of the WT or MyD88-KO BM-derived cells in non-GVHD hosts. It was also revealed that MyD88-KO CD11b+Gr-1+ cells preferred differentiation into CD11c+ dendritic cells (DCs) to expansion as myeloid-derived suppressor cells in GVHD hosts or in high inflammatory in vitro conditions. These CD11c+ DCs comprised the majority of MyD88-KO CD11b+Gr-1+ apoptotic cells in GVHD hosts. Their ability to cross-present alloantigens of host origin contributed to the enhancement of T cell alloreactivity, causing GVHD aggravation and eventually death through the killing function of activated T cells. These results provide insights into the roles of MyD88 in myelopoiesis of donor BM and the protective effects in GVHD hosts, helpful information for development of a strategy to control GVHD.

The Effect of Catechin on Physical Properties of Outer Membranes Cultured from Porphyromonas Gingivalis

성기수,김태영,주지민,김다솔,장혜옥 대한구강악안면병리학회 2023 대한구강악안면병리학회지 Vol.47 No.2

Fluorescent probe were used to evaluate the effects of catechin on the structural parameters (annular lipid fluidity, transbilayer lateral and rotational mobility and protein clustering) of the Porphyromonas gingivalis outer membrane (OPGs). An experimental procedure was used on the basis of selective quenching of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py and DPH. Catechin increased the bulk lateral and rotational mobility, annular lipid fluidity of OPGs lipid bilayers, and had greater fluidizing efficacy on the outer monolayer than the inner monolayer. It also caused membrane proteins to cluster. Based on these effects of catechin on OPGs, the antibacterial and antiviral actions of catechin can be partially explained.

Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow

임지영,이영관,이성은,주지민,박경신,최은영,민창기 대한면역학회 2015 Immune Network Vol.15 No.3

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88- deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of CD11b+Gr-1+ myeloidderived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88- deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.

Chlorhexidine digluconate가 세균외막과 인공세포막의 회전운동에 미치는 비대칭적 영향

김태영,차성권,엄승일,배문경,배수경,주지민,윤일희,김다솔,장혜옥 대한구강악안면병리학회 2021 대한구강악안면병리학회지 Vol.45 No.3

Chlorhexidine is a cationic bisbiguanide with broad antibacterial activity, and diverse activity encompassing gram-positive and gram-negative bacteria, yeasts, dermatophytes, and some lipophilic viruses. Chlorhexidine alters the permeability of the bacterial membrane. They also neutralize periodontal pathogens such as Streptococcus aureus, Porphyromonas gingivalis, and Prevotella intermedia. Porphyromonas gingivalis were cultured to isolate the Porphyromonas gingivalis outer membranes (OPG). Also, OPG were used to prepare large unilamellar liposomes with total lipids (OPGTL) extracted and prepared with the phospholipids mixture (PL). The effect of chlorhexidine digluconate on cell membrane kinetic changes was investigated using fluorescence polarization of n-(9-anthroyloxy) stearic acid with different rotational mobility depending on the probe substitution position (n) in the membrane phospholipid aliphatic chain. Chlorhexidine digluconate increased the hydrocarbon rotational mobility interior of the OPG, OPGTL and PL, but native and model membranes interfacial mobility were decreased. The sensitivity to increasing chlorhexidine digluconate effect on rotational mobility was proportional to the depth of probe position in descending order of 16-AP, 12-AS, 6-AS and 9-AS. Chlorhexidine digluconate disordering or ordering the effects on the membrane lipids may cause its bacteriostatic and bacteriocidal actions.

A Case of Invasive Pulmonary Aspergillosis with Direct Invasion of the Mediastinum and the Left Atrium in an Immunocompetent Patient

한규현,김은경,김정현,신선영,정혜윤,주지민,김학수,김대진,심민정,조상호 대한결핵및호흡기학회 2014 Tuberculosis and Respiratory Diseases Vol.77 No.1

We report a case of invasive pulmonary aspergillosis invading the mediastinum and the left atrium. A 70-year-old woman was hospitalized for dyspnea. She had been well controlled for her diabetes mellitus and hypertension. The chest X-ray disclosed mediastinal widening, and the computed tomography scan of the chest showed that there was a large mediastinal mass and this lesion extended into the left atrium and right bronchus. The cardiac echocardiography showed that a huge mediastinal cystic mass compressed in the right atrium and a hyperechoic polypoid lesion in the left. The pathology from the bronchoscopic biopsy observed abundant fungal hyphae which was stained with periodic acid-Schiff and Gomori's methenamine silver. Despite the treatment with antifungal agents, she died from cardiac tamponade after three months. Invasive pulmonary aspergillosis, which involves the mediastinum and the heart, is very rare in immunocompetent patients.