Immunologic analysis of patients with postinfectious bronchiolitis obliterans

Purpose@#This study aimed to analyze the immunologic profile of children with postinfectious bronchiolitis obliterans (PIBO) in order to approach pathophysiology affected by host factors. @*Methods@#A total of 10 children with PIBO were prospectively enrolled. We obtained information on demographics from their caregiver and electric medical records. Peripheral blood samples were collected before cyclic systemic methylprednisolone therapy and complete blood count, immunoglobulin level and lymphocyte subset were analyzed. @*Results@#The white blood cell count and immunoglobulin level were within the normal range in children with PIBO. The CD4+/CD8+ ratio was not significantly different from those of the healthy control group. A decreased proportion of both central memory T cells (median [interquartile range]; 13.5% [8.3%–16.3%] vs. 18.5% [15.9%–24.1%], P = 0.01) and effector memory T cells (10.3% [5.0%–18.4%] vs. 20.9% [16.6%–26.3%], P = 0.03) in CD4+T cells was observed in the PIBO group compared with those in the control group. In CD8+T cells, the proportion of effector memory T cells (7.8% [4.2%–13.8%] vs. 24.3% [15.3%–27.9%], P = 0.02) and CD45RA+effector memory T cells (16.2% [11.0%–36.6%] vs. 24.2% [17.1%–39.7%], P = 0.04) was decreased in the patient group compared with the control group. @*Conclusion@#It is suggested that T lymphocyte subset abnormalities may be associated with a decrease in the ability to differentiate the T cells immediately upon reinfection and induce an effective response to infection. These results may partially explain the pathophysiological individual vulnerabilities to PIBO after lower respiratory tract infections in children.

T Cell-Specific Knockout of STAT3 Ameliorates Dextran Sulfate Sodium-Induced Colitis by Reducing the Inflammatory Response

Signal transducer and activator of transcription 3 (STAT3) has a crucial role in various autoimmune disorders including, inflammatory bowel disease (IBD). Our previous study demonstrated that STAT3 activation by IL-6 in colonic epithelial cells exacerbates experimental ulcerative colitis. Activated T lymphocytes are also found in ulcerative colitis patients with intestinal inflammation, but the role of STAT3 in T cells remains elusive. To determine the STAT3 function of T cells in intestinal inflammation, we generated T cell-specific STAT3 knockout (KO) mice and used dextran sulfate sodium (DSS) to induce colitis. In this study, we demonstrated that T cell-specific STAT3 deletion alleviated DSS-induced colitis in mice, resulting in reduced histological scores and myeloperoxidase (MPO) activity. Importantly, the population of T cells in the spleen and lymph nodes was significantly decreased in the control and DSS-induced groups of STAT3 KO mice. In addition, STAT3 deficiency in T cells markedly reduced the production of interferon (IFN)-γ, IL-6, and IL-17A, whereas IL-10 secretion was increased. Collectively, the results suggest that STAT3 in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.

The Analysis of Vitamin C Concentration in Organs of Gulo-/- Mice Upon Vitamin C Withdrawal

BACKGROUND: Vitamin C is an essential nutrient for maintaining human life. Vitamin C insufficiency in the plasma is closely related with the development of scurvy. However, in vivo kinetics of vitamin C regarding its storage and consumption is still largely unknown. METHODS: We used Gulo-/- mice, which cannot synthesize vitamin C like human. Vitamin C level in plasma and organs from Gulo-/- mice was examined, and it compared with the level of wild-type mice during 5 weeks. RESULTS: The significant weight loss of Gulo-/- mice was shown at 3 weeks after vitamin C withdrawal. However, there was no differences between wild-type and vitamin C-supplemented Gulo-/- mice (3.3 g/L in drinking water). The concentration of vitamin C in plasma and organs was significantly decreased at 1 week after vitamin C withdrawal. Vitamin C is preferentially deposited in adrenal gland, lymph node, lung, and brain. There were no significant changes in the numbers and CD4/CD8 ratio of splenocytes in Gulo-/- mice with vitamin C withdrawal for 4 weeks. And the architecture of spleen in Gulo-/- mice was disrupted at 5 weeks after vitamin C withdrawal. CONCLUSION: The vitamin C level of Gulo-/- mice was considerably decreased from 1 week after vitamin C withdrawal. Vitamin C is preferentially stored in some organs such as brain, adrenal gland and lung.

Identification of CM1 as a Pathogenic Factor in Inflammatory Diseases and Cancer

BACKGROUND: CM1 (centrocyte/-blast marker 1) was defined by a mAb against concanavalin A (Con A) activated PBMC. It is expressed in germinal center of human tonsil and on the surface of activated PBMC as well as cancer cells. Recently, increased productions of pro-inflammatory mediators were detected from activated PBMC by CM1 ligation. METHODS: However, there is a limitation to explain the exact role of CM1 on inflammation and its related mechanisms, since the identity of CM1 is still not clarified. In our previous study, we have already confirmed that soluble form of CM1 was produced by Raji. Therefore, we performed Q-TOF analysis after immunoprecipitation of concentrated Raji culture supernatant using anti-CM1 mAbs. RESULTS: As a result, we found that CM1 is identical to enolase-1(ENO1), a glycolytic enzyme, and we confirmed that results by silencing ENO1 using siRNA. It was also confirmed through competition assay between anti-CM1 and anti-ENO1 mAbs. Finally, we investigated the possible role of CM1 in inflammatory response and cancer. The ligation of CM1 on Raji cells with anti-CM1 mAbs induces the extensive production of prostaglandin E2(PGE2). In addition, the increased activity of matrix metalloproteinase (MMP)-2/9 was shown in NCI-N87, stomach cancer cell line by CM1 stimulation. CONCLUSION: CM1 is identical to ENO1 and it might be an important role in the regulation of inflammatory responses.

Scrub Typhus in a Pregnant Woman: No Evidence of Intrauterine Infection / 감염

Pregnancy with scrub typhus is a rare condition. A 30-year-old woman was infected with scrub typhus at the 35th week of gestation. She was treated successfully with azithromycin, and delivered her baby uneventfully. The baby developed no signs for scrub typhus, and thrived well. IgM antibodies to O. tsutsugamushi were undetectable in the baby's sera, and titers of IgG antibodies did not rise. The polymerase chain reaction of the cord blood for O. tsutsugamushi was also negative. We concluded that transplacental infection did not occur in this pregnant woman.

Seroepidemiological Survey of Hemorrhagic Fever with Renal Syndrome in Korea , 1994 - 1996

To understand the seroepidemiological patterns of haemorrhagic fever with renal syndrome in Korea, a nation-wide survey collaborated with fourteen clinics was carried out from 1994 to 1996. Sera of 4,547 patients with acute febrile episodes were tested by indirect immunofluorescent antibody test and the seroepidemiological analysis including sex, age, seasonal and regional distributions were performed. According to the results obtained in this study, the epidemiological characteristics of haemorrhagic fever with renal syndrome in Korea were summarized as follows: 1. Seropositive rate of hemorrhagic fever with renal syndrome among the patients with acute febrile episodes was 6.4% by the cut-off point of 1:40. 2. Among the seropositives, male outnumbered female and the ratio of males to females was 2.0:1.0. 3. Seventy six % of the seropositive patients were 21-60 years old. 4. The number of seropositive cases increased from October and reached maximum in December and began to decrease gradually from January. 5. The geographical distribution of the seropositives cover most areas including Cheju province in Korea.

Infectivity of Orientia tsutsugamushi to Various Eukaryotic Cells and Their Cellular Invasion Mechanism

Orientia tsutsugamushi is obligate intracellular bacterium that grows within the cytoplasm of the eukaryotic host cells. Therefore capability of the attachment, entry into the host cell and intracellular survival should be critical process for oriential infection. In this study we investigated the cellular invasion mechanism of Orientia tsutsugamushi and the role of transmembrane heparan sulfate proteoglycan, which binds diverse components at the cellular microenvironment and is implicated as host cell receptors for a variety of microbial pathogens. First of all Orientia tsutsugamushi can invade a wide range of nonprofessional phagocytic cells including fibroblast, epithelial cells a#nd endothelial cells of various host species, including B and T lymphocytes. Thus, it was postulated that the attachment of O. tsutsugamushi requires the recognition of ubiquitous surface structures of many kinds of host cells. Treatments with heparan sulfate and heparin inhibited the infection of Orientia tsutsugamushi in dose-dependent manner for L cell, mouse fibroblast, whereas other glycosaminoglycans such as chondroitin sulfate had no effect. Collectively, these findings provide strong evidence that initial interaction with heparan sulfate proteoglycan is required for the oriential invasion into host cells.

Molecular Cloning of the Major Immunogen of Orientia tsutsugamushi Thai Strains and Development Passive Hemagglutination Test

The 56-kilodalton protein genes of Orientia tsutsugamushi TA678, TA686, TA716, TA763 strains were amplified by PCR. The amplified products were sequenced and cloned into pIH821 vector. The recombinant proteins were expressed in Escherichia coli as fusion proteins with maltose binding protein. The recombinant proteins were purified and used for the sensitization of sheep RBCs and the reactivity of the recombinant 56-kDa proteins of Orientia tsutsugamushi TA 678, TA686, TA716 strains were analyzed with 40 sera from scrub typhus patients in Korea, 40 sera from scrub typhus in Thailand, Malaysia and Philippines. The 56-kDa protein coding DNA sequence of Orientia tsutsugamushi TA678, TA686, TA716 show 70 to 88% homology with other known strains and four variable regions are also observed. 39 of 40 sera from scrub typhus patients in Korea showed the strongest reactivity to the recombinant protein of Boryong strain and one sera showed the strongest reactivity to the recombinant protein of Gilliam strain. 14 of 40 sera from patients in Thailand, Malaysia and Philippines showed the strongest reactivity to the recombinant protein of TA686 strain and 12 sera showed the strongest reactivity to the recombinant protein of TA716 strain. No serum from patients in Thailand, Malaysia and Philippines showed the strongest reactivity to the recombinant protein of Boryong strain.

Mapping of Phorbol Ester and Calcium Ionophore - Responsive Sequence Element in the c - jun Promoter in Activated T Cells / 대한면역학회지

No abstract available.