bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?
Authors: Martins M Â , Silva M L , Marciano A P V , Peruhype-Magalhães V , Eloi-Santos S M , Ribeiro J G L , Correa-Oliveira R , Homma A , Kroon E G , Teixeira-Carvalho A , Martins-Filho O A 
Published: August 2010

SummaryOver past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broad-based immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19+interleukin(IL)10R+/CD19+CD32+) at day 15. Increased frequency of CD4+human leucocyte antigen D-related(HLA-DR+) at day 7 and CD8+HLA-DR+ at day 30 suggest distinct kinetics of T cell activation, with CD4+ T cells being activated early and CD8+ T cells representing a later event following 17DD vaccination. Up-regulation of modulatory features on CD4+ and CD8+ cells at day 15 seems to be the key event leading to lower frequency of CD38+ T cells at day 30. Taken together, our findings demonstrate the co-existence of phenotypic features associated with activation events and modulatory pathways. Positive correlations between CD4+HLA-DR+ cells and CD4+CD25high regulatory T cells and the association between the type 0 chemokine receptor CCR2 and the activation status of CD4+ and CD8+ cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature.
Mannan-binding lectin is a determinant of survival in infective endocarditis
Authors: Tran C T , Kjeldsen K , Haunsø S , Høiby N , Johansen H K , Christiansen M 
Published: August 2010

Summary
Mannan-binding lectin (MBL) is a collectin plasma protein activating the lectin pathway of the complement system, enhancing opsonophagocytosis and modulating the cytokine response to inflammation. Deficiency of MBL, caused by structural mutations or promoter polymorphisms in the MBL2 gene, has been associated with increased susceptibility to infection and autoimmune disease. Thus, as infective endocarditis remains a severe disease requiring intensive and long-term treatment with antibiotics, we examined whether there was an association between MBL and clinical outcome in 39 well-characterized patients with infective endocarditis. Five patients (13%) had MBL concentrations &lt; 100 µg/l and were considered MBL-deficient. This proportion was similar to that in a healthy control group of blood donors. Mortality 3 months after diagnosis was 20% in patients with MBL-deficiency and 9% in patients with normal MBL. The 5-year mortality was 80% and 25%, respectively. MBL-deficiency was on univariate survival statistics associated with significantly higher mortality on follow-up (P = 0·03). In conclusion, this is the first report of an association between MBL-deficiency and survival in infective endocarditis. The present observation is important, as replacement therapy in MBL-deficient patients is possible. For certain high-risk subgroups, it opens new perspectives for improvement of treatment and outcome in infective endocarditis.
Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study
Authors: Pertovaara M , Raitala A , Juonala M , Lehtimäki T , Huhtala H , Oja S S , Jokinen E , Viikari J S A , Raitakari O T , Hurme M 
Published: August 2010

SummaryIndoleamine 2,3 dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, suppresses T cell activity and is up-regulated by various inflammatory stimuli. The ratio of kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp) reflects IDO activity. We calculated IDO activity and measured carotid intima-media thickness (IMT), a presymptomatic predictor of atherosclerosis, in 986 young adults (544 female, 442 male) for whom data on levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, high sensitive C-reactive protein (CRP), body mass index (BMI), waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure and smoking habits were available. IDO activity correlated significantly with IMT in female subjects, but not in males. In a multivariate linear regression model, IDO did not correlate independently with IMT in female subjects. However, IDO activity correlated significantly with several risk factors for atherosclerosis in females, i.e. with age, LDL-C, BMI, weakly with CRP and inversely with HDL-C and triglyceride. In males IDO activity correlated significantly with CRP and inversely with HDL-C. In conclusion, our results suggest that the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females.
Increased CD11b expression on polymorphonuclear leucocytes and cytokine profiles in patients with Kawasaki disease
Authors: Kobayashi T , Kimura H , Okada Y , Inoue Y , Kobayashi T , Shinohara M , Morikawa A 
Published: August 2010

SummaryClinical evidence implicates polymorphonuclear leucocytes in the pathogenesis of vasculitis in Kawasaki disease. We examined modulation of expression of adhesion molecules (CD11b and CD62L) on polymorphonuclear leucocytes and how this expression is related to serum cytokine concentrations. In 18 patients with Kawasaki disease and 15 control subjects, adhesion molecule expression was determined by two-colour immunofluorescence staining of blood leucocytes and flow cytometry. Eight cytokines and chemokines were also measured. In patients with Kawasaki disease, mean fluorescence intensity for CD11b before giving intravenous immunoglobulin was significantly higher than in normal subjects (P &lt; 0·005). After intravenous immunoglobulin, mean fluorescence intensity for CD11b decreased significantly. With coronary artery lesions present, mean CD11b fluorescence intensity was significantly higher than without coronary artery lesions (P = 0·005 before intravenous immunoglobulin; P = 0·024 after intravenous immunoglobulin). No differences were seen in CD62L expression on polymorphonuclear leucocytes between patients with Kawasaki disease and normal subjects. CD11b expression on polymorphonuclear leucocytes correlated positively with serum interleukin (IL)-6, IL-10, granulocyte colony-stimulating factor, percentage of neutrophils among white cells and C-reactive protein. Polymorphonuclear leucocytes from patients with Kawasaki disease showed increased CD11b expression, which was associated with increased serum cytokines and appeared to be related to coronary artery lesions.
Different temporal expression of immunodominant Ro60/60 kDa-SSA and La/SSB apotopes
Authors: Reed J H , Neufing P J , Jackson M W , Clancy R M , Macardle P J , Buyon J P , Gordon T P 
Published: August 2010

SummaryOpsonization of apoptotic cardiocytes by maternal anti-Ro/SSA and anti-La/SSB antibodies contributes to tissue injury in the neonatal lupus syndrome. The objective of the current study was to quantify the surface membrane expression of Ro/La components during different phases of apoptosis and map the Ro/La apotopes (epitopes expressed on apoptotic cells) bound by cognate antibodies. Multi-parameter flow cytometry was used to define early and late apoptotic populations and their respective binding by monospecific anti-Ro and anti-La IgGs. Anti-Ro60 bound specifically to early apoptotic Jurkat cells and remained accessible on the cell surface throughout early and late apoptosis. In contrast, anti-La bound exclusively to late apoptotic cells in experiments controlled for non-specific membrane leakage of IgG. Ro52 was not accessible for antibody binding on either apoptotic population. The immunodominant NH2-terminal and RNA recognition motif (RRM) epitopes of La were expressed as apotopes on late apoptotic cells, confirming recent in vivo findings. An immunodominant internal epitope of Ro60 that contains the RRM, and is recognized by a majority of sera from mothers of children with congenital heart block (CHB) and patients with primary Sjögren's syndrome, was also accessible as an apotope on early apoptotic cells. The distinct temporal expression of the immunodominant Ro60 and La apotopes indicates that these intracellular autoantigens translocate independently to the cell surface, and supports a model in which maternal antibody populations against both Ro60 and La apotopes act in an additive fashion to increase the risk of tissue damage in CHB.
Antibody CR1-2B11 recognizes a non-polymorphic epitope of human CR1 (CD35)
Authors: Chen C-H , Ghiran I , Beurskens F J M , Weaver G , Vincent J A , Nicholson-Weller A , Klickstein L B 
Published: August 2010

SummaryMeasurement of erythrocyte [red blood cells (RBC)] complement receptor type 1 (CR1, CD35) has the potential to serve as a sensitive assessment of complement activation and immune complex clearance. All previously reported monoclonal antibodies (MoAb) to the extracellular region of CR1 recognize epitopes within the long homologous repeats (LHR) of CR1 and the epitopes for the most frequently used MoAbs are repeated at least twice per CR1 molecule. Furthermore, CR1 exhibits structural polymorphism characterized by a variable number of LHR per molecule. Thus, accurate enumeration of cell surface CR1 using currently available MoAb would require that the results be corrected for the number of antibody epitopes per CR1 molecule encoded by each individual's alleles. To obtain a MoAb to a non-polymorphic epitope on human CR1, hybridomas were generated from mice immunized with recombinant soluble CR1 (sCR1) and MoAb were screened for those that recognized the full-length extracellular domain but failed to bind to all four recombinant LHR fragments. A single antibody, CR1-2B11, was identified and was found to recognize an epitope located wholly within SCR29-30 of CR1, NH2-terminal to an elastase cleavage site. Like other CR1 MoAb, the CR1-2B11 epitope expression decreased on old erythrocytes compared to younger cells and CR1-2B11 did not identify a CR1 ‘stump’ on RBC. Importantly, CR1-2B11 immunofluorescence did not change with storage or handling of RBC, unlike the apparent decrease in immunofluorescence observed with other MoAb. CR1-2B11 should be useful for the accurate enumeration of RBC CR1.
Effector T lymphocytes in well-nourished and malnourished infected children
Authors: Nájera O , González C , Cortés E , Toledo G , Ortiz R 
Published: August 2010

Summary
The mechanisms involved in impaired immunity in malnourished children are not well understood. CD4+ CD62L– and CD8+ CD28– do not express the naive cell markers CD62L and CD28, suggesting that they function as effector T cells. Using a flow cytometry-based analysis we examined the proportions of CD4+ CD62L– and CD8+ CD28– T cell subsets in well-nourished infected (WNI) and malnourished infected (MNI) children. Here we report that WNI children had a higher percentage of CD4+ CD62L– (11·1 ± 1·0) and CD8+ D28– (40·2 ± 5·0) T cell subsets than healthy (6·5 ± 1·0 and 23·9 ± 4·8) and MNI children (7·4 ± 1·1 and 23·1 ± 6·2, respectively) (P &lt; 0·5). Data suggest that WNI children respond efficiently against pathogenic microbes. In contrast, relatively low numbers of circulating of CD4+ CD62L– and CD8+ CD28– T cells in MNI children may represent an ineffective response to infection. Levels of effector T cells in children with gastrointestinal infections versus those suffering from respiratory infections were also significantly different within the WNI group. While WNI children with gastrointestinal infections had higher absolute and relative values of CD8+, and CD8+ CD28– T subsets, by those with respiratory infections had higher values of CD4+ lymphocytes. However, due to the small number of subjects examined, our results in WNI children should be interpreted with caution and confirmed using a larger sample size. Our data suggest that altered expression of CD62L and CD28 receptors may contribute to impaired T cell function observed in MNI children.
Newly recruited human monocytes have a preserved responsiveness towards bacterial peptides in terms of CD11b up-regulation and intracellular hydrogen peroxide production
Authors: Dadfar E , Jacobson S H , Lundahl J 
Published: August 2010

SummaryThe transmigration of peripheral human monocytes to the interstitium is a fundamental step in the host-defence mechanism against infections. Little is known about the state of function of in vivo transmigrated interstitial monocytes prior to differentiation into macrophages and dendritic cells. We hypothesized that newly recruited interstitial monocytes have a preserved responsiveness against bacterial-related peptides, giving them a specific role in the immediate defence against invading pathogens. In order to test this hypothesis, we explored the responsiveness of in vivo transmigrated as well as peripheral monocytes, in terms of CD11b expression and H2O2 production towards the bacterial-related peptide formylmethionylleucylphenylalanine (fMLP) by the use of a skin chamber technique. In addition, we analysed the concentration of interleukin (IL)-8, monocyte chemotactic protein-1 (MCP-1) and tumour necrosis factor (TNF)-α in the skin blister exudates and in the circulation. We demonstrate that in vivo-transmigrated monocytes had a fivefold higher CD11b expression compared to monocytes obtained from the peripheral circulation. fMLP exposure induced a significantly higher CD11b expression on transmigrated cells compared to peripheral monocytes. In addition, newly recruited monocytes had a preserved H2O2 production. The interstitial concentration of IL-8, MCP-1 and TNF-α was significantly higher in blister exudates compared to that in the peripheral circulation. Thus, in vivo transmigrated human monocytes preserve their capacity to respond towards bacterial peptides in terms of CD11b up-regulation and H2O2 generation. These data strengthen a role for newly recruited interstitial human monocytes in the immediate defence against invading pathogens.
Pre-incubation with interleukin-4 mediates a direct protective effect against the loss of pancreatic β-cell viability induced by proinflammatory cytokines
Authors: Kaminski A , Kaminski E R , Morgan N G 
Published: August 2010

SummaryLoss of pancreatic β-cells in type I diabetes is associated with an increase in T helper 1 (Th1) proinflammatory cytokines in the islet milieu, with a concomitant reduction in Th2 anti-inflammatory cytokines. In animal models, manoeuvres designed to polarize Th1 responses towards Th2, particularly involving interleukin (IL)-4, have been shown to protect against insulitis and diabetes. The aim of this study was to determine whether IL-4 can exert a direct effect on β-cell viability. The rat pancreatic β-cell line, BRIN-BD11, was used. IL-4R mRNA expression was assayed by reverse transcription–polymerase chain reaction and DNA sequencing and protein expression measured using anti-IL-4R antibodies and confocal microscopy. Cells were pretreated in vitro with IL-4, incubated with IL-1β and interferon (IFN)-γ and DNA fragmentation and nitrite production analysed by flow cytometry and Griess assay, respectively. Expression of type I (IL-4R alpha and common γ-chain) and type II (IL-4R alpha, IL-13R alpha-1) IL-4R mRNA transcripts, together with cell surface expression of IL-4R, was demonstrated. Pre-incubation with IL-4 reduced significantly cell death induced by IL-1β alone or by a combination of IL-1β and IFN-γ, although this was not accompanied by a reduced production of nitrite. The protective effect of IL-4 was not seen when all three cytokines were added simultaneously. These results demonstrate, for the first time, expression of IL-4 receptor components on rat pancreatic β-cells and reveal a direct protective effect on the loss of viability mediated by proinflammatory cytokines when β-cells are pre-incubated with IL-4.
Anti-β1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease
Authors: Labovsky V , Smulski C R , Gómez K , Levy G , Levin M J 
Published: August 2010

SummaryChronic Chagas heart disease (cChHD), a chronic manifestation of the Trypanosoma cruzi infection, is characterized by high antibody levels against the C-terminal region of the ribosomal P proteins (i.e. peptide R13, EEEDDDMGFGLFD) which bears similarity with the second extracellular loop of β1-adrenergic receptor (β1-AR, peptide H26R HWWRAESDEARRCYNDPKCCDFVTNR). Because it has not been demonstrated clearly that IgGs from cChHD patients bind to native human β1-AR, the aim of this study was to investigate further the physical interaction between cChHD IgGs and the human β1-AR. Immunofluorescence assays demonstrated the binding of these antibodies to the receptor expressed on stably transfected cells, together with a β1-AR agonist-like effect. In addition, immunoadsorption of the serum samples from cChHD patients with a commercially available matrix, containing peptides representing the first and the second extracellular loop of the β1-AR, completely abolished reactivity against the H26R peptide and the physiological response to the receptor. The follow-up of this specificity after in vitro immunoadsorption procedures suggests that this treatment might be used to diminish significantly the serum levels of anti-β1-AR antibodies in patients with Chagas heart disease.
Role of the mucosal integrin αE(CD103)β7 in tissue-restricted cytotoxicity
Authors: Smyth L J C , Kirby J A , Cunningham A C 
Published: August 2010

SummaryThe effectiveness of lung transplantation is marred by the relatively high incidence of rejection. The lung normally contains a large population of lymphocytes in contact with the airway epithelium, a proportion of which expresses the mucosal integrin, αE(CD103)β7. This integrin is not a homing receptor, but is thought to retain lymphocytes at the epithelial surface. Following transplantation, a population of ‘tissue-restricted’ cytotoxic T cells (CTL) have been identified which have the ability to lyse epithelial cells, but not major histocompatibility complex (MHC)-identical splenic cells. We tested the hypothesis that expression of the mucosal integrin confers the ability of CTL to target and destroy e-cadherin expressing targets. Immunohistochemical and flow cytometric analyses were used to demonstrate the relevance of this model to human lung. Allo-activated CTL were generated in mixed leucocyte reactions and CD103 expression up-regulated by the addition of transforming growth factor (TGF)-β. The functional effect of CD103 expression was investigated in 51Cr-release assays using e-cadherin-expressing transfectant targets. Human lung epithelial cells express e-cadherin and one-third of intraepithelial lymphocytes (IEL) expressed CD103. Allo-activated and bronchoalveolar lavage (BAL) lymphocytes express more CD103 than those in blood. Transfection of e-cadherin into murine fibroblasts conferred susceptibility to lysis by αEβ7-expressing CTL which could be blocked by specific monoclonal antibodies to CD103 and e-cadherin. CD103 functions to conjugate CTL effectors to e-cadherin-expressing targets and thereby facilitates cellular cytotoxicity. E-cadherin is expressed prominently by epithelial cells in the lung, enabling CTL to target them for destruction.
Identification of a diagnostic antibody-binding region on the immunogenic protein EpC1 from Echinococcus granulosus and its application in population screening for cystic echinococcosis
Authors: Zhang W-B , Li J , Li Q , Yang D , Zhu B , You H , Jones M K , Duke M , McManus D P 
Published: August 2010

Summary
An Echinococcus granulosus cDNA sequence coding for EpC1, a proven serodiagnostic marker for cystic echinococcosis (CE, hydatid disease), has high amino acid sequence identity to a paralogue from Taenia solium, the cause of neurocysticercosis (NCC). To determine diagnostic antibody-binding regions on EpC1 recognized specifically by CE sera, 10 truncated regions (P1–10) of the immunogenic protein were expressed in Escherichia coli and subjected to immunoblotting. One peptide, designated peptide 5 [P5, fused with glutathione-S-transferase (GST)] was positively recognized by sera from mice experimentally infected with oncospheres of E. granulosus and sera from surgically confirmed CE patients. Sera from NCC patients did not react with any of the peptides used. There are four amino acid substitutions in P5 compared with the T. solium sequence and these may form part of the epitope inducing CE-specific antibody. Ninety-seven per cent (58 of 60) of sera from confirmed CE patients recognized P5-GST, which was higher than the parent EpC1 fused with GST which reacted with 92% (55 of 60) of the sera. A population screening survey showed that 424 human sera collected from communities in Xinjiang, an area in China endemic for CE, exhibited 4·5% and 3·3% positivity in immunoblotting analysis to EpC1 and P5, respectively; 19·8% of these sera reacted positively against hydatid cyst fluid (HCF) antigen B. Low numbers of surgical CE cases have been reported from this population, suggesting that HCF-based serology lacks specificity and that EpC1 or its contained P5 peptide may prove more accurate for seroepidemiological surveys of CE.
Proportion of peripheral blood and decidual CD4+ CD25bright regulatory T cells in pre-eclampsia
Authors: Sasaki Y , Darmochwal-Kolarz D , Suzuki D , Sakai M , Ito M , Shima T , Shiozaki A , Rolinski J , Saito S 
Published: August 2010

SummaryCD4+ CD25bright regulatory T (Treg) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4+ CD25bright Treg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3+) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25bright cells within the CD4+ T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P &lt; 0·001) and non-pregnant healthy controls (P &lt; 0·001). Also, the percentage of FoxP3+ cells within CD3+ T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of Treg cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.