bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered phenotype and function of dendritic cells in children with type 1 diabetes
Authors: Angelini F , Del Duca E , Piccinini S , Pacciani V , Rossi P , Manca Bitti M L 
Published: September 2005

SummaryThe importance of dendritic cells (DC) in the activation of T cells and in the maintenance of self-tolerance is well known. We investigated whether alterations in phenotype and function of DC may contribute to the pathogenesis of Type 1 diabetes (T1DM). Mature DC (mDC) from 18 children with T1DM and 10 age-matched healthy children were tested. mDC, derived from peripheral blood monocytes cultured for 6 days in presence of interleukin (IL)-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) and stimulated with lipopolysaccharide (LPS) for the last 24 h, were phenotyped for the expression of the co-stimulatory molecules B7·1 and B7·2. In six patients and six controls allogenic mixed leucocyte reaction (AMLR) was performed using mDC and cord blood-derived naive T cells at a DC/T naive ratio of 1 : 200. Proliferation was assessed on day 7 by [3H]-thymidine incorporation assay. Mature DC derived from patients showed, compared with controls, a reduced expression of B7·1 [mean of fluorescence intensity (MFI): 36·2 ± 14·3 versus 72·9 ± 34·5; P = 0·004] and B7·2 (MFI: 122·7 ± 67·5 versus 259·6 ± 154·1; P = 0·02). We did not find differences in the HLA-DR expression (P = 0·07). Moreover, proliferative response of allogenic naive T cells cultured with mDC was impaired in the patients (13471 ± 9917·2 versus 40976 ± 24527·2 cpm, P = 0·04). We also measured IL-10 and IL-12 concentration in the supernatant of DC cultures. Interestingly, we observed in the patients a sevenfold higher level of IL-10 (P = 0·07) and a ninefold lower level of IL-12 (P = 0·01). Our data show a defect in the expression of the co-stimulatory molecules and an impairment of DC priming function, events that might contribute to T1DM pathogenesis.
Temporal cytokine gene expression patterns in subjects with trachoma identify distinct conjunctival responses associated with infection
Authors: Faal N , Bailey R L , Sarr I , Joof H , Mabey D C W , Holland M J 
Published: September 2005

SummaryOcular chlamydial disease is clinically diagnosed by the appearance of characteristic inflammatory changes and development of lymphoid follicles in the conjunctiva. Nucleic acid amplification tests and relatively non-invasive methods of sampling the conjunctival surface can be used to quantify the expression of chlamydial and host genes. Using quantitative real-time polymerase chain reaction to detect the presence of Chlamydia trachomatis (CT) 16S rRNA and human interleukin (IL)-1β, IL-10, IL-12p40, interferon (IFN)-γ and tumour necrosis factor (TNF)-α transcripts we examined the immune response at the conjunctival surface in a cohort of children living in a trachoma-endemic village in The Gambia. Elevated cytokine transcript levels were associated with the presence of CT 16S rRNA. Subclinical infection (CT infection without clinical signs of disease) elicited an immune response that is proinflammatory in nature, with elevations in the transcription of IL-1β, IFN-γ and IL-12p40. Clinically apparent infections were associated with the elevation of mRNA for the multi-functional cytokine TNF-α (fibrotic, type 1 inflammatory and regulatory) and the counter regulatory cytokine, IL-10, in addition to the other proinflammatory cytokines. A positive correlation between IFN-γ transcript levels and the amount of CT 16S rRNA expressed in conjunctiva was found.
Molecular manipulation with the arthritogenic epitopes of the G1 domain of human cartilage proteoglycan aggrecan
Authors: Murad Y M , Szabó Z , Ludányi K , Glant T T 
Published: September 2005

SummarySystemic immunization of BALB/c mice with human cartilage proteoglycan (PG) aggrecan induces progressive polyarthritis. The G1 domain of the PG aggrecan molecule contains most of the T cell epitopes, including three immunodominant (‘arthritogenic’) and at least six subdominant T cell epitopes. The three dominant T cell epitopes (P49, P70 and P155) were deleted individually or in combination by site directed mutagenesis, and the recombinant human G1 (rhG1) domain (wild type and mutated) proteins were used for immunization. Close to 100% of BALB/c mice immunized with the wild-type (nonmutated) rhG1 domain developed severe arthritis, which was 75% in the absence of P70 (5/4E8) epitope, and very low (&lt; 10% incidence) when all three dominant T cell epitopes were deleted. The onset was delayed and the severity of arthritis reduced in animals when dominant T cell epitopes were missing from the immunizing rhG1 domain. The lack of T cell response to the deleted epitope(s) was specific, but the overall immune response against the wild-type rhG1 domain of human PG was not significantly affected. This study helped us to understand the dynamics and immune-regulatory mechanisms of arthritis, and supported the hypothesis that the development of autoimmune arthritis requires a concerted T cell response to multiple epitopes, rather than the immune response to a single arthritogenic structure.
Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine
Authors: Martinuč Porobič J , Avčin T , Božič B , Kuhar M , Čučnik S , Zupančič M , Prosenc K , Kveder T , Rozman B 
Published: September 2005

Summary
This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti-cardiolipin antibodies (aCL), antibodies against β2GPI (anti-β2GPI), lupus anti-coagulant (LA), anti-nuclear antibodies and antibodies against extractable nuclear antigens (anti-ENA). The study population consisted of 85 healthy students (63 female, 22 male; mean age 20·8 years), vaccinated with three doses of recombinant DNA hepatitis B vaccine. One month after vaccination with the first dose of hepatitis B vaccine a minority of vaccinated individuals showed changes in IgG or IgM aCL or anti-β2GPI or LA activity (P &lt; 0·001). Among subjects in whom changes of IgG anti-β2GPI were observed, a significantly higher number of increased (8/85) than decreased (2/85) values were found (P &lt; 0·01). Analyses of paired data showed that differences in aCL or anti-β2GPI levels before vaccination or 1 month later did not reach statistical significance. In two people aCL transitorily reached medium positivity after the first dose of hepatitis B vaccine with a drop 5 months later. Similar evident anti-β2GPI fluctuation was also observed in one person. Another participant was initially low positive for IgG anti-β2GPI and the levels were increasing after vaccination. Two participants became positive for anti-nuclear antibodies during 6 months’ follow-up. There were no sex-dependent differences in tested antibodies observed and no associations between levels of aPL and levels of anti-HBV antibodies. We conclude that HBV can induce aPL, although rarely. In genetically susceptible individuals or together with some other triggers such combination might confer the risk of developing a continuous autoimmune response in an individual.
Cellular immunity in healthy volunteers treated with an octavalent conjugatePseudomonas aeruginosavaccine
Authors: Zuercher A W , Imboden M A , Jampen S , Bosse D , Ulrich M , Chtioui H , Lauterburg B H , Lang A B 
Published: September 2005

SummaryHumoral immunity in response to an octavalent O-polysaccharide-toxin A conjugate Pseudomonas aeruginosa vaccine is well studied, and a Phase III clinical study in cystic fibrosis (CF) patients is currently ongoing. In contrast, little is known about cellular immunity induced by this vaccine. Fifteen healthy volunteers were immunized on days 1 and 60. Parameters of cellular immunity were studied before vaccination on day 1, and on day 74. Analyses included flow cytometry of whole blood, and antigen-induced proliferation of and cytokine production by lymphocyte cultures. The effects of immunization on the composition of peripheral blood lymphocytes as determined by flow cytometry were minor. In contrast, after immunization a highly significant increase of proliferation in response to stimulation with detoxified toxin A was noted: the stimulation index rose from 1·4 on day 1 to 42·2 on day 74 (restimulation with 0·4 µg/ml; P = 0·003). Immunization led to significant production of interferon (IFN)-γ and tumour necrosis factor (TNF)-α by antigen-stimulated lymphocytes. In contrast, no significant induction of interleukin (IL)-4 or IL-10 was observed. In conclusion, immunization of healthy volunteers led to activation of cellular immunity including strong antigen-specific proliferation and cytokine production. In CF patients priming of the cellular immune system towards a Th1-like pattern would be of potential advantage. Therefore, confirmatory analyses in immunized CF patients with and without chronic infection with P. aeruginosa are foreseen.
Dancing with the enemy: the interplay of herpes simplex virus with dendritic cells
Authors: Novak N , Peng W M 
Published: September 2005

Summary
Herpes simplex virus (HSV) represents a smart pathogen, which displays both lytic and latent modes of interaction with its natural human host. In order to be optimally equipped for immune evasion and to reply to any attacks of the host during reactivation, HSV has developed a multitude of cleverly devised defence strategies. Dendritic cells (DC) as antigen-presenting cells located at the border zones of the body and the environment have been shown to play a crucial role as one of the first cells interacting with HSV beside epithelial cells, on one hand, and as important controllers of the viral spreading on the other hand. Here, we provide a research update about the interaction of HSV with DC and summarize the latest proceedings in this field.
Stable, soluble, high-affinity, engineered T cell receptors: novel antibody-like proteins for specific targeting of peptide antigens
Authors: Boulter J M , Jakobsen B K 
Published: September 2005

SummaryThe recent development of T cell receptor phage display opens up the possibility of engineering human T cell receptors with antibody-like binding properties for cell-surface peptide antigens. In this review we briefly discuss recent developments in molecular targeting of peptide antigens. We then discuss potential clinical applications of engineered high-affinity T cell receptors in autoimmunity and cancer.
Defective signalling in salivary glands precedes the autoimmune response in the non-obese diabetic mouse model of sialadenitis
Authors: Rosignoli F , Roca V , Meiss R , Leceta J , Gomariz R P , Pérez Leirós C 
Published: September 2005

Summary
The spontaneous non-obese diabetic (NOD) mouse model of Sjögren's syndrome provides a valuable tool to study the onset and progression of both the autoimmune response and secretory dysfunction. Our purpose was to analyse the temporal decline of salivary secretion in NOD mice in relation to the autoimmune response and alterations in various signalling pathways involved in saliva secretion within each salivary gland. A progressive loss of nitric oxide synthase activity in submandibular and parotid glands started at 12 weeks of age and paralleled the decline in salivary secretion. This defect was associated with a lower response to vasoactive intestinal peptide in salivary flow rate, cAMP and nitric oxide/cGMP production. No signs of mononuclear infiltrates or local cytokine production were detectable in salivary glands in the time period studied (10–16 weeks of age). Our data support a disease model for sialadenitis in NOD mice in which the early stages are characterized by defective neurotransmitter-mediated signalling in major salivary glands that precedes the autoimmune response.
Correlations among measles virus-specific antibody, lymphoproliferation and Th1/Th2 cytokine responses following measles–mumps–rubella-II (MMR-II) vaccination
Authors: Dhiman N , Ovsyannikova I G , Ryan J E , Jacobson R M , Vierkant R A , Pankratz V S , Jacobsen S J , Poland G A 
Published: September 2005

SummaryImmunity to measles is conferred by the interplay of humoral and cellular immune responses, the latter being critical in maintaining long-term recall response. Therefore, it is important to evaluate measles-specific humoral and cellular immunity in populations several years after vaccination and understand the correlations among these measures of immunity. We examined measles-specific antibodies, lymphoproliferation and the Th1/Th2 signature cytokines, interferon (IFN)-γ and interleukin (IL)-4, in a population-based cohort of healthy children from Olmsted County, Minnesota after two doses of measles–mumps–rubella-II (MMR-II) vaccine. We detected positive measures of measles-specific cellular and humoral immunity in the majority of our study population. However, a small proportion of subjects demonstrated an immune response skewed towards the Th2 type, characterized by the presence of either IL-4 and/or measles-specific antibodies and a lack of IFN-γ production. Further, we observed a significant positive correlation between lymphoproliferation and secretion of IFN-γ (r = 0·20, P = 0·0002) and IL-4 (r = 0·15, P = 0·005). Measles antibody levels were correlated with lymphoproliferation (r = 0·12, P = 0·03), but lacked correlation to either cytokine type. In conclusion, we demonstrated the presence of both long-term cellular and humoral responses after MMR-II vaccination in a significant proportion of study subjects. Further, a positive correlation between lymphoproliferation and IL-4 and IFN-γ suggests that immunity to measles may be maintained by both Th1 and Th2 cells. We speculate that the Th2 biased response observed in a subset of our subjects may be insufficient to provide long-term immunity against measles. Further examination of the determinants of Th1 versus Th2 skewing of the immune response and long-term follow-up is needed.
Selective expansion of CD16highCCR2– subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation
Authors: Mizuno K , Toma T , Tsukiji H , Okamoto H , Yamazaki H , Ohta K , Ohta K , Kasahara Y , Koizumi S , Yachie A 
Published: September 2005

SummaryMonocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16highCCR2– subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16highCCR2– monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16lowCCR2+ subpopulation produced little. These results were contrary to the generally accepted notion that the CD16highCCR2– monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16highCCR2– subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16highCCR2– subpopulations are of a distinct lineage from CD16lowCCR2+ monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.
The association of anti-phospholipid antibodies with parity in placental malaria
Authors: Owens S , Chamley L W , Ordi J , Brabin B J , Johnson P M 
Published: September 2005

SummaryAnti-phospholipid antibodies (aPL) are autoantibodies associated with both infections and the pathogenesis of certain pregnancy complications. In the latter, but not the former, aPL are dependent on a co-factor, β2 glycoprotein I (β2GPI), which can also be used as an antigen for detection of such aPL in pregnancy. A cross-sectional study was carried out on serum samples from Kumasi, Ghana, to determine the occurrence and β2GPI-dependence of aPL in placental malaria. Anti-cardiolipin, anti-phosphatidylserine and anti-β2GPI enzyme-linked immunosorbent assays (ELISAs) were performed on sera from 103 HIV-non-infected gravid women. Placental malaria, both active and past infection, was diagnosed in 33/103 (32%) based on placental histology. In multiparae, β2GPI-independent IgM antibodies to cardiolipin (P = 0·018) and phosphatidylserine (P = 0·009) were observed, which were most pronounced in past placental malaria infection. In primiparae, no association emerged between aPL and placental malaria. Trends for improved clinical parameters were identified in infected women with levels of anti-cardiolipin beyond the 99th multiple of the median for a healthy, non-malarious population. This study in placental malaria reports parity associations of β2GPI-independent aPL profiles, and does not support a role for β2GPI-dependent aPL. It is of significance in the context of the known parity differences in pregnancy malaria immunity.
Modelling the basin‐scale demography of Calanus finmarchicus in the north‐east Atlantic
Authors: SPEIRS DOUGLAS C. , GURNEY WILLIAM S.C. , HEATH MICHAEL R. , WOOD SIMON N. 
Published: September 2005

AbstractIn this paper, we report on a coupled physical–biological model describing the spatio‐temporal distribution of Calanus finmarchicus over an area of the North Atlantic and Norwegian Sea from 56°N, 30°W to 72°N, 20°E. The model, which explicitly represents all the life‐history stages, is implemented in a highly efficient discrete space–time format which permits wide‐ranging dynamic exploration and parameter optimization. The underlying hydrodynamic driving functions come from the Hamburg Shelf‐Ocean Model (HAMSOM). The spatio‐temporal distribution of resources powering development and reproduction is inferred from SeaWiFS sea‐surface colour observations. We confront the model with distributional data inferred from continuous plankton recorder observations, overwintering distribution data from a variety of EU, UK national and Canadian programmes which were collated as part of the Trans‐Atlantic Study of Calanus (TASC) programme, and high‐frequency stage‐resolved point time‐series obtained as part of the TASC programme. We test two competing hypotheses concerning the control of awakening from diapause and conclude that only a mechanism with characteristics similar to photoperiodic control can explain the test data.
Spatial patterns of genetic structure among populations of a stone‐cased caddis (Trichoptera: Tasimiidae) in south‐east Queensland, Australia
Authors: SCHULTHEIS ALICIA S. , HUGHES JANE M. 
Published: September 2005

Summary1. Gene flow and dispersal among populations of a stone‐cased caddis (Tasimiidae: Tasimia palpata) were estimated indirectly using a 460 bp region of the cytochrome oxidase I gene of mitochondrial DNA.2. There was no significant differentiation at the largest spatial scale (between catchments) and no correlation between genetic distance and geographic distance. These results are consistent with widespread adult dispersal.3. Conversely, significant genetic differentiation was detected at the smallest spatial scale examined (among reaches within streams). This pattern was primarily because of significant FST values in a single stream (Bundaroo Creek).4. Bundaroo Creek also had the lowest mean number of haplotypes per population (n = 7) suggesting that a limited number of females may be responsible for recruitment at these sites. Significant FST's at the reach scale may be a result of this ‘patchy’ recruitment. However, additional evidence regarding the long‐range dispersal ability and fecundity of T. palpata females is needed to test this hypothesis fully.
Problems in using statistical analysis of replacement and silent mutations in antibody genes for determining antigen‐driven affinity selection
Authors: Bose Biplab , Sinha Subrata 
Published: September 2005

SummaryThe analysis of molecular signatures of antigen‐driven affinity selection of B cells is of immense use in studies on normal and abnormal B cell development. Most of the published literature compares the expected and observed frequencies of replacement (R) and silent (S) mutations in the complementarity‐determining regions (CDRs) and the framework regions (FRs) of antibody genes to identify the signature of antigenic selection. The basic assumption of this statistical method is that antigenic selection creates a bias for R mutations in the CDRs and for S mutations in the FRs. However, it has been argued that the differences in intrinsic mutability among different regions of an antibody gene can generate a statistically significant bias even in the absence of any antigenic selection. We have modified the existing statistical method to include the effects of intrinsic mutability of different regions of an antibody gene. We used this method to analyse sequences of several B cell‐derived monoclonals against T‐dependent antigens, T‐independent antigens, clones derived from lymphoma and amyloidogenic clones. Our sequence analysis indicates that even after correcting for the intrinsic mutability of antibody genes, statistical parameters fail to reflect the role of antigen‐driven affinity selection in maturation of many clones. We suggest that, contrary to the basic assumption of such statistical methods, selection can act both for and against R mutations in the CDR as well as in the FR regions. In addition we have identified different methodological difficulties in the current uses of such statistical analysis of antibody genes.
Lipopolysaccharide‐induced elevation and secretion of interleukin‐1β in the submandibular gland of male mice*
Authors: Yao Chenjuan , Li Xuefei , Murdiastuti Kwartarini , Kosugi‐Tanaka Chisato , Akamatsu Tetsuya , Kanamori Norio , Hosoi Kazuo 
Published: September 2005

SummaryThe intraperitoneal injection of lipopolysaccharide (LPS) (400 µg/kg body weight) induced the expression of mRNAs of inflammatory cytokines such as interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α in the submandibular gland (SMG) of C3H/HeN mice but not that of C3H/HeJ mice, a mutant strain for Toll‐like receptor‐4 (TLR‐4– mutant). The mRNA levels of these cytokines in the SMG of the wild‐type mice increased as early as 3 hr after injection, peaked at 3–6 hr, and had decreased again by 24 hr. In this study, we particularly focused on IL‐1β, and induction by this endotoxin was investigated in detail. Denervation of the superior cervical trunk and chorda tympani nerve did not diminish the LPS‐induced elevation of IL‐1β mRNA in the SMG, indicating the irrelevance of the central nervous system in this induction. TLR‐4 mRNA and protein were shown to be strongly expressed in the SMG, suggesting the direct action of LPS on this gland. IL‐1β proteins were localized in the secretory granules of granular convoluted tubular (GCT) cells, and their molecular weights in the gland were 17·5 and 20 kDa. IL‐1β of the same size appeared in the saliva 6 hr after LPS injection in C3H/HeN but not in C3H/HeJ mice. The present study thus suggests that IL‐1β, an inflammation cytokine, is induced and secreted into the saliva in response to endotoxin injected intraperitoneally.