bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of insects on primary production in temperate herbaceous communities: a meta‐analysis
Authors: Coupe Malcolm D. , Cahill James F.
Published: September 2003

Abstract. 1. The effects of insects on primary production in temperate herbaceous communities were investigated in a meta‐analysis. The following hypotheses were tested: (1) the effect of insects on primary production depends on community type, (2) the effect of insects on primary production varies as a function of productivity, (3) insects have a greater effect on primary production in communities with low species diversity, and (4) insects have a larger effect on primary production during outbreaks.

2. Data were collected from 24 studies in which insecticides were used to suppress insects in self‐sown or pastoral communities. Effect sizes were calculated from sprayed and control plot standing crop or yield, expressed as the log response ratio, ln (sprayed plot phytomass/control plot phytomass).

3. There was a significant increase in primary production as a result of insect suppression. Forb‐dominated communities showed a more variable response than graminoid communities. During outbreaks, insects had a greater negative impact on primary production. Effect size was unaffected by productivity or plant species richness.

4. Although insects lower primary production in a diversity of temperate herbaceous communities, the basic measures by which such communities are often described have little effect on the proportional impact that insects have on primary production. While outbreaks are significant predictors of higher negative impact on primary production, causes of outbreaks are not always related to traits of the plant community.
Movement patterns ofRhyssomatus lineaticollisSay (Coleoptera: Curculionidae) within and amongAsclepias syriaca(Asclepiadaceae) patches in a fragmented landscape
Authors: St Pierre Matthew J. , Hendrix Stephen D.
Published: September 2003

Abstract. 1. Dispersal capabilities of organisms are critical in determining the landscape population structure of species as well as their likelihood of survival in fragmented landscapes. Using mark–recapture techniques on the monophagous weevilRhyssomatus lineaticollisSay (Curculionidae), within‐ and between‐patch dispersal capabilities, landscape level population structure, and the role of beetle density and host patch characteristics in setting distances, amounts, and timing of dispersal were studied.

2. The data indicate thatR. lineaticollisis sedentary, with 50% of recaptured beetles moving < 1 m and the maximum distance moved < 1 km. Within‐ and between‐patch movement of beetles was unrelated to host plant patch characteristics and beetle densities.

3. Despite limited dispersal,R. lineaticollisprobably functions as a patchy population in east‐central Iowa, U.S.A. because dispersals between patches are common and because all host patches surveyed contained this herbivore, indicating a lack of suitable vacant patches, a prerequisite for metapopulation structure.

4. Between‐patch distances are well within the dispersal capabilities ofR. lineaticollis, although this may be the result of an increase in the density of patches of its host,Asclepias syriaca, in the landscape over the last 150 years as a result of human disturbance and this species' weedy habit.

5. Metapopulation structure in monophagous prairie herbivores may be most likely in species whose non‐weedy host plants form highly predictable resources in space and time, but which are now widely scattered in habitat fragments.
Effect of emigration on cannibalism and intraguild predation in aphidophagous ladybirds
Authors: Sato Satoru , Dixon Anthony F. G. , Yasuda Hironori
Published: September 2003

Abstract.  1. The incidence and timing of emigration, cannibalism, and intraguild predation of larvae of three aphidophagous ladybirds (Coleoptera: Coccinellidae), Harmonia axyridis Pallas, Coccinella septempunctata brucki Mulsant, and Propylea japonica Mulsant, relative to the presence of prey was determined in the laboratory in single‐ and mixed‐species populations.

2. In single‐species populations, 80% of the larvae of C. s. brucki emigrated prior to the extinction of the aphid population and no larvae were lost due to cannibalism; however > 80% of the larvae of the other two species were still present when the aphid became extinct and the losses due to cannibalism for H. axyridis and P. japonica were 25% and 14% respectively. Finally, 28% of the P. japonica larvae completed their development, whereas no larvae of the other two species became adult.

3. In mixed‐species populations, mortality of P. japonica attributable to cannibalism or intraguild predation increased greatly to 60%, whereas that of the other two species remained about the same. Consequently, survival of H. axyridis larvae improved and survival of P. japonica worsened; however the survival of C. s. brucki larvae was not affected by the other two species. Early emigration by C. s. brucki larvae may have enabled them to escape intraguild predation by H. axyridis in this system.
Interactions with native mosquito larvae regulate the production of Aedes albopictus from bromeliads in Florida
Authors: Lounibos L. P. , O'Meara G. F. , Nishimura N. , R. L. Escher
Published: September 2003

Abstract. 1. Immatures of the invasive container mosquito Aedes albopictus occur in water‐holding tanks and axils of ornamental bromeliads in Florida, where this species established and became abundant in the late 1980s and early 1990s.

2. The numbers of A. albopictus in bromeliads in gardens vary geographically in Florida, being significantly higher in northern sites where two species of Wyeomyia mosquitoes, native specialists of this microhabitat, are absent.

3. Causes of the negative relationship between abundances of A. albopictus and Wyeomyia spp. were investigated experimentally using Billbergia pyramidalis, an introduced bromeliad popular in Florida gardens.

4. Egg laying by A. albopictus in B. pyramidalis confined in a large outdoor cage was unaffected by the presence or absence of Wyeomyia spp. fourth instars, indicating that immatures of the native bromeliad mosquito species do not deter oviposition by the invasive species in this microhabitat.

5. Growth and survivorship of A. albopictus first instars in tanks of B. pyramidalis were negatively affected by the presence of fourth instar, but not first instar, Wyeomyia spp. larvae at natural densities. Stimulative effects of leaf litter on A. albopictus growth and survivorship in this microhabitat were independent of the presence or absence of Wyeomyia spp. immatures.

6. These results demonstrate that interspecific larval interactions regulate the production and explain the geographic patterns in abundance of A. albopictus from ornamental bromeliads in Florida.
Impact of avian and arthropod predation on lepidopteran caterpillar densities and plant productivity in an ephemeral agroecosystem
Authors: Hooks Cerruti R. R. , Pandey Raju R. , Johnson Marshall W.
Published: September 2003

Abstract.  1. Most studies evaluating the combined impact of spiders and other predators on herbivore densities in agroecosystems have focused primarily on their trophic connections with invertebrate predators (e.g. carabids, chrysopids); however linkages among spiders and vertebrate predators may also help structure the population dynamics of insect herbivores. A field experiment was conducted to examine the impact of avian and spider predation on lepidopteran caterpillar densities and plant productivity within a Brassica agroecosystem.

2. Arthropod abundance, leaf‐chewing damage, and final plant productivity associated with broccoli, Brassica oleracea L. (var. italica), were recorded for four treatments: (1) bird present but spiders removed; (2) both birds and spiders present; (3) birds excluded, spiders present; and (4) birds and spiders both excluded.

3. Densities of Artogeia rapae L. (Lepidoptera: Pieridae) and Trichoplusia ni Hübner (Lepidoptera: Noctuidae) large caterpillars and post feeding stages were reduced significantly by bird predation. The abundance of large caterpillars was also reduced on spider‐inhabited plants during early plant growth; however the assemblage of birds and spiders did not suppress caterpillar densities more significantly than either predator alone.

4. Plants protected by birds, spiders, and birds plus spiders sustained less folivory attributable to leaf chewing caterpillars than check plants. Plant productivity was also greater for predator‐protected plants than check plants.

5. Although spiders and parasitoids were responsible for some of the mortality inflicted upon lepidopteran caterpillars, it was concluded that in this study system, birds are the most important natural enemies of folivores.
The distribution and species characteristics of the Culicoides biting midge fauna of South Africa
Authors: Rawlings P. , Meiswinkel R. , Labuschange K. , Welton N. , Baylis M. , Mellor P. S.
Published: September 2003

Abstract.  1. Monthly light trap collections over 2 years at 39 sites across South Africa captured over 3 000 000 Culicoides of 86 species, some of them known vectors of African horse sickness and bluetongue viruses.

2. To aid disease control and risk evaluation, cluster analysis and association measurements were carried out on species present at each site. Six species occurred at almost all sites. From the remaining 80 species, eight clusters were identified at > 48% similarity.

3. Culicoides citroneus and C. krameri were characteristic of cluster 8, C. loxodontis of cluster 4, and two numbered, but un‐named, species, C. #119 and C. #89, of cluster 5.

4. Multiple anova and multiple discriminant analysis on the climatic and geographic parameters of sites in each cluster gave two significant discriminant functions that explained 91.5% of the variance between clusters. Function 1 contrasted sites with high cold cloud duration and high vegetation index with sites with high wind speeds. Function 2 contrasted upland clusters that also had high cold cloud duration with hotter, lower altitude sites.

5. Species associations were explained in terms of biotic provinces, based on ecogeographic factors that have previously been useful to describe communities of birds.

6. None of the clusters was ideal for siting an African horse sickness‐vector free quarantine station as C. imicola and C. bolitinos, the main vectors, were found in all clusters but in very low abundance in cluster 5. The analysis provides a firm basis for studying the changing patterns of species distribution under varying climatic influences.
Influence of host plant heterogeneity on the distribution of a birch aphid
Authors: Johnson Scott N. , Elston David A. , Hartley Susan E.
Published: September 2003

Abstract.  1. The spatial and temporal abundance of the aphid Euceraphis betulae was investigated in relation to heterogeneity in host plant (Betula pendula) vigour and pathogenic stress. The performance of aphids feeding on vigorous and stressed foliage was also examined.

2. The plant stress and plant vigour hypotheses have been suggested as opposing ways in which foliage quality influences herbivore abundance. In many plants, however, vigorous growing foliage co‐exists with stressed or damaged foliage.

3. There was a negative correlation between branch growth (vigour) and branch stress (leaf chlorosis), with the most vigorous branches displaying little or no stress, and the most stressed branches achieving poor growth. There was a similar negative correlation between vigour and stress at the level of individual trees, which themselves represented a continuum in quality.

4. At the beginning of the season, E. betulae were intermittently more abundant on vigorous branches than on branches destined to become stressed, but aphids became significantly more abundant on stressed branches later in the season, when symptoms of stress became apparent. Similar patterns of aphid abundance were seen on vigorous and stressed trees in the following year.

5. Euceraphis betulae performance was generally enhanced when feeding on naturally stressed B. pendula leaves, but there was some evidence for elevated potential reproduction when feeding on vigorous leaves too.

6. Overall, plant stress probably influences E. betulae distribution more than plant vigour, but the temporal and spatial variability in plant quality suggests that plant vigour could play a role in aphid distribution early in the season.
Are honey bees' foraging preferences affected by pollen amino acid composition?
Authors: Cook Samantha M. , Awmack Caroline S. , Murray Darren A. , Williams Ingrid H.
Published: September 2003

Abstract.  1. Although pollen is a vital nutritional resource for honey bees, Apis mellifera, the influence of pollen quality on their foraging behaviour is little understood.

2. In choice‐test experiments, bees showed no innate pollen‐foraging preferences, but preferred oilseed rape Brassica napus pollen over field bean Vicia faba pollen after previous foraging experience of oilseed rape.

3. The free amino acid content of oilseed rape and field bean pollen was compared using high‐performance liquid chromatography. Oilseed rape pollen contained a greater proportion of the most essential amino acids required by honey bees (valine, leucine, and isoleucine) than field bean, suggesting that oilseed rape pollen is of greater nutritional quality for honey bees than is field bean pollen.

4. Honey bee foraging preferences appeared to reflect pollen quality. The hypothesis that pollen amino acid composition affects the foraging behaviour of honey bees is discussed.
Habitat edges as a potential ecological trap for an insect predator
Authors: Ries Leslie , Fagan William F.
Published: September 2003

Abstract.  1. Ecological traps, where animals actively select poor habitat for reproduction over superior habitat, are generally associated with birds at forest edges. This study examines oviposition preference, predation, and parasitism rates in the mantid Stagmomantis limbata to determine the potential generality of this phenomenon.

2. Egg case (oothecae) densities were measured across two edge types (cottonwood and desert scrub) within desert riparian ecosystems. A positive edge effect in oothecae density was found with an approximate three‐fold increase in density at cottonwood (Xedge = 0.05 oothecae/100 m2 vs. Xinterior = 0.015 oothecae/100 m2) and desert scrub (Xedge = 0.20 oothecae/100 m2 vs. Xinterior = 0.06 oothecae/100 m2) edges (P < 0.01).

3. Rates of bird predation were significantly higher for oothecae at desert scrub edges and showed a trend of higher predation rates at cottonwood edges, suggesting that riparian habitat edges may be acting as an ecological trap for this mantid species. There was no effect of edges on oothecal parasitism rates.

4. These results provide an example of the effect of habitat edges on a generalist insect predator and indicate that an ecological trap may exist with respect to one of its natural enemies.
Gall size determines the structure of theRabdophaga strobiloideshost–parasitoid community
Authors: Van Hezewijk Brian H. , Roland Jens
Published: September 2003

Abstract. 1. The relationship between gall size and mortality of the willow pinecone gall midgeRabdophaga strobiloides(Diptera: Cecidomyiidae) was examined by determining the fate of all galls in a 30‐ha area in central Alberta, Canada over 4 years. It was found that gall size has a large effect on the type and intensity of mortality experienced by the gall midge, and consequently this factor has the potential to influence the dynamics of the host–parasitoid interaction through the creation of phenotypic refuges.

2. Total midge mortality ranged from 51% to 78% over the course of the study and was dominated by parasitism byTorymus cecidomyiae(Hymenoptera: Torymidae) andGastrancistrussp. (Hymenoptera: Pteromalidae) as well as predation by birds. Gall size had a strong, non‐linear effect on the attack rates of each of these natural enemies.

3. Birds attacked the smallest size classes.Torymus cecidomyiaepreferentially attacked medium diameter galls and thus avoided predation by birds in smaller galls.Gastrancistrussp. preferentially attacked the largest galls and consequently suffered lower rates of predation by bothT. cecidomyiaeand birds.

4. This study emphasises the importance of understanding the interactions among mortality factors in order to describe adequately the susceptibility ofR. strobiloidesto parasitism and predation, and ultimately its population dynamics.
Apoptosis induction by interleukin‐2‐activated cytotoxic lymphocytes in a squamous cell carcinoma cell line and Daudi cells – involvement of reactive oxygen species‐dependent cytochrome c and reactive oxygen species‐independent apoptosis‐inducing factors
Authors: Yamamoto Tetsuya , Ueta Eisaku , Osaki Tokio
Published: September 2003

Investigation of the induction of apoptosis by cytotoxic lymphocytes has mainly focused on the signalling associated with Fas and its adaptor proteins. The signal pathway via mitochondria, however, has not been sufficiently elucidated in cytotoxic lymphocyte‐induced apoptosis. We examined the release of mitochondrial proapoptotic factors by lymphokine‐activated killer (LAK) cells in two cell lines. LAK cell‐induced DNA fragmentation of the target cells was suppressed to approximately 50% of control levels by the addition of neutralizing monoclonal antibody to Fas and a granzyme B inhibitor. When intracellular reactive oxygen species (ROS) were scavenged, the LAK cell‐induced DNA fragmentation was decreased to approximately 60% of the non‐treated cell level. Co‐cultivation of Daudi cells with LAK cells increased cytosolic and mitochondrial ROS levels. Activation of procaspase‐3 and apoptosis by treatment of oral squamous cell carcinoma cells (OSC) with LAK cells was partially inhibited by pretreatment of OSC cells with ROS scavengers and mitochondrial complex inhibitors. Furthermore, cytochrome c and apoptosis‐inducing factor (AIF) were released from mitochondria by OSC cell treatment with supernatants of LAK cells. The supernatant‐induced cytochrome c release was suppressed by mitochondrial complex inhibitors, but the inhibitors did not inhibit the release of AIF. These results indicate that LAK cells induce target cell apoptosis via not only the Fas/Fas ligand system and granzyme B, but also ROS‐dependent cytochrome c and ROS‐independent AIF release.
A Salmonella typhi OmpC fusion protein expressing the CD154 Trp140–Ser149 amino acid strand binds CD40 and activates a lymphoma B‐cell line
Authors: Vega Mario I. , Santos‐Argumedo Leopoldo , Huerta‐Yepez Sara , Luría‐Perez Rosendo , Ortiz‐Navarrete Vianney , Isibasi Armado , González‐Bonilla Cesar R.
Published: September 2003

CD154 is a type II glycoprotein member of the tumour necrosis factor (TNF) ligand family, which is expressed mainly on the surface of activated T lymphocytes. The interaction with its receptor CD40, plays a central role in the control of several functions of the immune system. Structural models based on the homology of CD154 with TNF and lymphotoxin indicate that binding to CD40 involves three regions surrounding amino acids K143, R203 and Q220, and that strands W140–S149 and S198–A210 are critical for such interactions. Also, it has been reported that two recombinant CD154 fragments, including amino acid residues Y45–L261 or E108–L261 are biologically active, whereas other polypeptides, including S149–L261, are not. Therefore, we decided to construct a fusion protein inserting the W140‐S149 amino acid strand (WAEKGYYTMS) in an external loop of the outer membrane protein C (OmpC) from Salmonella enterica serovar Typhi and assess its ability to bind CD40 and activate B cells. The sodium dodecyl sulphate–polyacrylamide gel electrophoresis demonstrated that the chimeric OmpC–gp39 protein conserved its ability to form trimers. Binding to CD40 was established by three variants of enzyme‐linked immunosorbent assay, a direct binding assay by coating plates with a recombinant CD40–Fc protein and through two competition assays between OmpC–gp39 and recombinant CD154 or soluble CD40–Fc. Flow cytometry analysis demonstrated that OmpC–gp39 increased the expression levels of major histocompatibility complex II, CD23, and CD80, in Raji human B‐cell lymphoma similarly to an antibody against CD40. These results further support that the CD154/CD40 interaction is similar to the TNF/TNF receptor. This is the first report of a bacterial fusion protein containing a small amino acid strand form a ligand that is able to activate its cognate receptor.
Selective regulation of CD40 expression in murine dendritic cells by thiol antioxidants
Authors: Iijima Norifumi , Yanagawa Yoshiki , Iwabuchi Kazuya , Onoé Kazunori
Published: September 2003

Interaction of CD40 on dendritic cells (DC) with CD40 ligand induces interleukin‐12 (IL‐12) production by these DC during the antigen presentation. Thus, the level of CD40 expression appears to influence the capability of DC to induce a T helper 1 (Th1) response. However, it is not fully understood how CD40 expression on DC is regulated. In the present study, we examined the effects of the reducing agents, N‐acetyl‐l‐cysteine (NAC) and reduced glutathione (GSH), on tumour necrosis factor‐α (TNF‐α)‐induced phenotypic changes in murine DC. TNF‐α markedly increased the expression on DC of major histocompatibility complex (MHC) and the costimulatory molecules, CD40, CD80 and CD86. Both NAC and GSH completely abolished the TNF‐α‐induced enhancement of CD40 expression, but had no considerable effect on the expression of CD80, CD86 and MHC. The marked decrease of CD40 protein with NAC was also detected by Western blotting, but was not associated with the expression level of CD40 mRNA in DC. Thus, NAC appears to reduce CD40 expression on DC by regulating a post‐transcriptional pathway. The inhibitory effect of NAC or GSH on TNF‐α‐induced CD40 expression was released by simply removing these agents from the culture. In contrast, culture of TNF‐α‐treated DC with NAC or GSH markedly decreased the expression of CD40 within 12 hr. These results demonstrate that reducing agents selectively, rapidly and reversibly regulate CD40 expression on DC, which may eventually affect the capability of DC for Th1/Th2 polarization.
Fas ligand‐induced murine pulmonary inflammation is reduced by a stable decoy receptor 3 analogue
Authors: Wortinger Mark A. , Foley Joseph W. , Larocque Patrick , Witcher Derrick R. , Lahn Michael , Jakubowski Joseph A. , Glasebrook Andrew , Song Ho Yeong
Published: September 2003

Fas ligand (FasL)‐induced lung inflammation has recently been suggested to play an important role in the pathogenesis of acute respiratory disease syndrome (ARDS). In order to further explore this connection, we established a FasL‐induced murine model of pulmonary inflammation. Instillation of recombinant FasL (rFasL) into the lung induced neutrophil infiltration and increased pulmonary permeability, as evidenced by increased total protein in the airspace; both occur in patients with ARDS. These effects were accompanied with a rapid induction of proinflammatory mediators: cytokine granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and the chemokines macrophage inflammatory protein‐2 (MIP‐2) and KC. Pretreatment with a FasL antagonist, a decoy receptor 3 analogue (DcR3 analogue), reduced neutrophil infiltration into the airspace and resulted in a highly significant reduction in the levels of GM‐CSF, MIP‐2 and KC in bronchoalveolar lavage (BAL) fluid. We postulate that rFasL may be responsible for induction of proinflammatory chemokines and cytokines in the lung, which in turn attract neutrophil infiltration into the airspace. This proinflammatory process and the associated pulmonary permeability may, in part, explain the association of FasL with severe pulmonary inflammation, such as ARDS, and shed new light on FasL and its role in lung injury.
Characterization of CC‐chemokine receptor 7 expression on murine T cells in lymphoid tissues
Authors: Bjorkdahl Olle , Barber Karen A. , Brett Sara J. , Daly Maria G. , Plumpton Christopher , Elshourbagy Nabil A. , Tite John P. , Thomsen Lindy L.
Published: September 2003

Expression of the lymph node homing and CC‐chemokine receptor 7 (CCR7), with L‐selectin (CD62L), has been shown to divide human memory T cells into two functionally distinct subsets. We generated a polyclonal antibody against murine CCR7 and used this antibody to study CCR7 expression on murine T‐cell subsets. Using flow cytometric staining of T cells for visualisation expression of CCR7 in association with CD62L and CD44, a major population of CD4 or CD8 T cells expressing CCR7 were found to be CD62Lhigh CD44low, which would suggest a naïve cell phenotype. By analogy with human studies, memory cells could be subdivided into CCR7high CD62Lhigh CD44high (central memory) and CCR7low CD62Llow CD44high (effector memory). The proportions of these populations were different in lymph node, blood and spleen. Functional, short‐term in vitro polyclonal stimulation of blood, spleen and lymph node cells from naive mice demonstrated that CCR7high CD4 T cells produced predominantly interleukin (IL)‐2, whereas CCR7low CD4 T cells produced both IL‐2 and interferon‐γ (IFN‐γ). However, in contrast to previously published reports, the CCR7high CD8 T‐cell subpopulation produced both IFN‐γ and IL‐2. Analysis of effector T cells, induced by immunization in vivo, showed that a proportion of activated naïve CD4 T cells down‐regulated CCR7 only after multiple cell divisions, and this coincided with the down‐regulation of CD62L and production of IL‐4 and IFN‐γ. Finally, analysis of effector T cells during the phase of maximal clonal expansion of secondary immune responses in vivo indicated that the vast majority of both IL‐2‐ and IFN‐γ‐producing cells are CCR7low, while few cytokine‐expressing CCR7high T cells were detected. Our results support the hypothesis, developed from studies with human cells, that CCR7 may separate functionally different murine memory T‐cell subpopulations, but indicate additional complexity in that CCR7high CD8 T cells also may produce IFN‐γ.
Phage display of human antibodies from a patient suffering from coeliac disease and selection of isotype‐specific scFv against gliadin
Authors: Rhyner Claudio , Weichel Michael , Hübner Philipp , Achatz Gernot , Blaser Kurt , Crameri Reto
Published: September 2003

Coeliac disease (CD), a gastrointestinal illness characterized by intestinal malabsorption, results from gluten intolerance accompanied with immunological responses towards gliadin, an ethanol‐soluble protein fraction of wheat and other cereals. The role of gliadin in eliciting immune responses in CD is still partly unclear; however, the occurrence of anti‐gliadin in the sera of patients suffering from CD correlates well with clinical symptoms. In this work we report the construction of isotype‐specific, phage‐displayed scFv libraries from peripheral blood lymphocytes of a patient with CD and from a healthy control individual. VH and VL chains were amplified by reverse transcription–polymerase chain reaction (RT–PCR) using a set of oligonucleotides recognizing all human variable gene families. The three scFv libraries (IgA, IgG and IgM) were selectively enriched for gliadin‐binding phage. After four rounds of affinity selection, polyclonal enrichment of gliadin‐binding phage was observed in all libraries from the CD patient but in none from the healthy donor. Phagemid particles generated from single clones were demonstrated to be gliadin‐specific, as shown by strongly positive enzyme‐linked immunosorbent assay (ELISA) and BiaCore signals. The VH and VL chains from samples of these monoclonal isotype‐specific phage were sequenced to identify the most common variable regions used by the immune system to elicit antibody responses against gliadin.
Simultaneous administration of a low‐dose mixture of donor bone marrow cells and splenocytes plus adenovirus containing the CTLA4Ig gene result in stable mixed chimerism and long‐term survival of cardiac allograft in rats
Authors: Jin Yongzhu , Zhang Qingyin , Hao JIE , Gao Xiang , Guo Yinglu , Xie Shusheng
Published: September 2003

T‐cell costimulatory blockade combined with donor bone marrow transfusion may induce mixed chimerism, rendering robust tolerance in transplanted organs and cells. However, most protocols entail high doses of donor bone marrow cells (BMCs) or repeated administration of costly agents that block costimulatory pathways, thus delaying clinical development. To circumvent these shortcomings, we developed a strategy in which the dosage of donor BMCs was reduced but compensated by donor splenocytes (SPLCs). Furthermore, repeated administration of costly agents was replaced with a single injection of adenovirus expressing a gene of interest. In rat cardiac transplantation models, cardiac allografts from DA (RT‐1a) rats were transplanted heterotopically into the abdomen of LEW (RT‐11) recipient rats. Immediately after cardiac transplantation, an adenovirus vector (AdCTLA4Ig; 5 × 109plaque‐forming units) containing the gene for CTLA4Ig was administered to recipients (n = 6) simultaneously with a low dose of donor BMCs (1 × 108/rat) and SPLCs (5 × 107/rat) via the portal vein. The treated LEW recipient rats developed long‐lasting mixed chimerism (>10% at >100 days) and exhibited long‐term cardiac allografts (mean survival time of > 200 days) compared with control recipients. Moreover, recipients displaying long‐lasting mixed chimerism accepted subsequent donor skin allografts while promptly rejecting third‐party skin allografts. These results suggest that blockade of the CD28‐B7 pathway, using adenovirus‐mediated CTLA4Ig gene transfer, in concert with a low dosage of donor BMCs and SPLCs, may represent a feasible strategy to induce stable mixed chimerism and permit long‐term survival of cardiac allografts.
Paradoxical effects of interleukin‐10 on the maturation of murine myeloid dendritic cells
Authors: Commeren Dianne L. , Van Soest Peter L. , Karimi Khalil , Löwenberg Bob , Cornelissen Jan J. , Braakman Eric
Published: September 2003

The immunoregulatory cytokine, interleukin‐10 (IL‐10), has been shown to inhibit the maturation of human myeloid dendritic cells (DC). In the present study, we demonstrate that IL‐10 has paradoxical effects on the maturation of murine myeloid bone marrow‐derived DC. On the one hand, IL‐10 inhibits the maturation of murine myeloid DC. The addition of IL‐10 to granulocyte–macrophage colony‐stimulating factor (GM‐CSF)‐supported murine BM‐derived DC cultures reduced the frequency of major histocompatibility complex (MHC) class IIbright cells. These IL‐10‐pretreated DC have a reduced capacity to stimulate T cells in an allogeneic mixed leucocyte reaction. On the other hand, however, and in contrast to the effects of IL‐10 on human DC, we found that the addition of IL‐10 from the initiation of the culture onwards induced an up‐regulation of the expression of the costimulatory molecules CD40, CD80 and CD86 on murine myeloid DC, as compared to DC generated with GM‐CSF only. Moreover, a subpopulation of IL‐10‐pretreated MHC class IIdim DC lacked the capacity to take up dextran‐fluorescein isothiocyanate (FITC), a feature of DC maturation. Taken together, our data demonstrate that the generation of murine myeloid DC in the presence of IL‐10 results in a population of incompletely matured MHC class IIdim CD80+ CD86+ DC. These DC lack T‐cell stimulatory capacity, suggesting a role for IL‐10 in conferring tolerogenic properties on murine myeloid DC.
Cytotoxic T‐cell responses to Mycobacterium bovis during experimental infection of cattle with bovine tuberculosis
Authors: Skinner Margot A. , Parlane Natalie , McCarthy Allison , Buddle Bryce M.
Published: September 2003

Cytotoxic T‐cell responses are thought to play a significant role in the host defence against mycobacterial infections. Little is understood about such responses of cattle to Mycobacterium bovis, the causative agent of bovine tuberculosis. The work described in this report demonstrates the activity of cytotoxic cells during experimental infection of cattle with M. bovis. The cytotoxic cells were found to have the ability to specifically lyse macrophages infected with M. bovis and were detected in peripheral blood lymphocytes after in vitro re‐exposure to M. bovis. Cytotoxic activity was detected 4 weeks after experimental infection with M. bovis; a similar level of activity was maintained during the infection and it was mediated by both WC1+γδ and CD8+ T cells. In addition, inhibition of the growth of M. bovis within infected macrophages was detected when they were exposed to cultures containing M. bovis‐specific cytotoxic cells. The ability to detect cytotoxic cells after infection of cattle with M. bovis will allow their activity to be measured during vaccination trials. Correlation of cytotoxic activity with disease outcome may aid in the design of new vaccines and vaccination strategies.
Induction of a protective capsular polysaccharide antibody response to a multiepitope DNA vaccine encoding a peptide mimic of meningococcal serogroup C capsular polysaccharide
Authors: Prinz Deborah M. , Smithson S. Louise , Kieber‐Emmons Thomas , Westerink M. A. Julie
Published: September 2003

Systemic infection by encapsulated organisms, such as Neisseria meningitidis, is a major cause of morbidity and mortality worldwide, especially in individuals less than 2 years of age. Antibodies directed at the capsular polysaccharide are shown to be protective against disease by inducing complement‐dependent bactericidal activity. The current polysaccharide vaccine has been shown to be poorly immunogenic in high‐risk groups and this is probably related to its T‐independent properties. An alternative approach to eliciting a T‐dependent serum immunoglobulin G (IgG) antibody response to encapsulated pathogens is DNA vaccination. We assessed the immunogenicity of a multiepitope DNA vaccine encoding a T‐cell helper epitope and a peptide mimic of N. meningitidis serogroup C. The DNA construct induced a significant anti‐polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C.
Decay‐accelerating factor induction by tumour necrosis factor‐α, through a phosphatidylinositol‐3 kinase and protein kinase C‐dependent pathway, protects murine vascular endothelial cells against complement deposition
Authors: Ahmad Saifur R. , Lidington Elaine A. , Ohta Rieko , Okada Noriko , Robson Michael G. , Davies Kevin A. , Leitges Michael , Harris Claire L. , Haskard Dorian O. , Mason Justin C.
Published: September 2003

We have shown that human endothelial cells (EC) are protected against complement‐mediated injury by the inducible expression of decay‐accelerating factor (DAF). To understand further the importance of DAF regulation, we characterized EC DAF expression on murine EC in vitro and in vivo using a model of glomerulonephritis. Flow cytometry using the monoclonal antibody (mAb) Riko‐3 [binds transmembrane‐ and glycosylphosphatidylinositol (GPI)‐anchored DAF], mAb Riko‐4 (binds GPI‐anchored DAF) and reverse transcription–polymerase chain reaction (RT–PCR), demonstrated that murine EC DAF is GPI‐anchored. Tumour necrosis factor‐α (TNF‐α) increased EC DAF expression, detectable at 6 hr and maximal at 24–48 hr poststimulation. DAF upregulation required increased steady‐state DAF mRNA and protein synthesis. In contrast, no increased expression of the murine complement receptor‐related protein‐Y (Crry) was seen with TNF‐α. DAF upregulation was mediated via a protein kinase C (PKC)α, phosphoinositide‐3 kinase (PI‐3 kinase), p38 mitogen‐activated protein kinase (MAPK) and nuclear factor‐κB (NF‐κB)‐dependent pathway. The increased DAF was functionally relevant, resulting in a marked reduction in C3 deposition following complement activation. In a nephrotoxic nephritis model, DAF expression on glomerular capillaries was significantly increased 2 hr after the induction of disease. The demonstration of DAF upregulation above constitutive levels suggests that this may be important in the maintenance of vascular integrity during inflammation, when the risk of complement‐mediated injury is increased. The mouse represents a suitable model for the study of novel therapeutic approaches by which vascular endothelium may be conditioned against complement‐mediated injury.
Retinoid‐ and carotenoid‐enriched diets influence the ontogenesis of the immune system in mice
Authors: Garcia Ada L. , Rühl Ralph , Herz Udo , Koebnick Corinna , Schweigert Florian J. , Worm Margitta
Published: September 2003

Vitamin A (VA) has been identified as an important factor for the development of the immune system, especially during ontogenesis. It has been shown that antibody secretion and proliferation of lymphocyte populations depend on retinoids. In the present study we investigated the influence of a base VA diet and diets enriched with VA, β‐carotene and lycopene, on the ontogenesis of the immune system in mice. We examined the absolute and relative concentrations of splenic B lymphocytes (CD45R/B220), T lymphocytes (CD3+) and their subpopulations (CD4+ and CD8+), and measured serum immunoglobulin G (IgG) concentrations in the offspring of supplemented dams at different ages (1, 3, 5, 7, 14, 21 and 65 days). The experimental diets resulted in higher numbers of T and B lymphocytes after VA and carotenoid enrichment, when compared, at various time‐points, with the base diet. Higher values of total serum IgG were found in the β‐carotene‐enriched diet group on day 7. On days 7 and 14, the enriched diets induced significant alterations in the percentages and total numbers of splenic lymphocytes in comparison to the base diet. Our results confirm that supplementation with VA and carotenoids affect the immune‐cell function during ontogenesis and suggest a possible role of these nutritional factors on the development of the immune system.
The MHC class I antigen presentation pathway: strategies for viral immune evasion
Authors: Hewitt Eric W.
Published: September 2003

Presumably because of the selective pressure exerted by the immune system, many viruses have evolved proteins that interfere with antigen presentation by major histocompatibility complex (MHC) class I molecules. These viruses utilize a whole variety of ingenious strategies to inhibit the MHC class I pathway. Viral proteins have been characterized that exploit bottlenecks in the MHC class I pathway, such as peptide translocation by the transporter associated with antigen processing. Alternatively, viral proteins can cause the degradation or mislocalization of MHC class I molecules. This is often achieved by the subversion of the host cell's own protein degradation and trafficking pathways. As a consequence elucidation of how these viral proteins act to subvert host cell function will continue to give important insights not only into virus–host interactions but also the function and mechanism of cellular pathways.
Heterogeneity and immunogenicity of theTrichinellaTSL‐1 antigen gp53
Authors: Romarís F. , Dea‐Ayuela M. A. , Bolás F. , Martínez‐Fernández A. R. , Sanmartín M. L. , Ubeira F. M.
Published: September 2003

This study investigates the heterogeneity and immunogenicity of theTrichinellaTSL‐1 antigen gp53. Western blotting analysis of severalTrichinellaisolates with the gp53‐specific monoclonal antibodies (mAbs) US5 and US9, produced in Btkxidmice, revealed that gp53 from the speciesT. britovi, T. murrelli andgenotype T8 had higher MW (60 kDa) than gp53 fromT. spiralis, T. nelsoni andgenotype T6 (53 kDa) and fromT. nativa(55 kDa). mAb US5 reacted only with gp53 fromT. spiralis.Experiments including immunoassays of gp53 binding by sera fromT. spiralis‐infected mice, in the presence of different potential inhibitors (recombinant gp53, US5,T. britovi‐crude larval extract (CLE), and CLEN‐ andO‐glycans), indicate (i) that gp53 fromT. spiralisbears specific epitopes that induce antibody formation during infection; (ii) that the protein epitopes of gp53 are much more important (76 or 68% of total antibody reactivity in BALB/c and Swiss CD‐1 mice, respectively) than the corresponding glycan epitopes including tyvelose (11 or 32% of total reactivity) for the induction of anti‐gp53 circulating antibodies; and (iii) that the species‐specific epitopes present on gp53 are differentially recognized in different mouse strains. Whereas in BALB/c mice US5‐ and non‐US5‐recognized species‐specific epitopes on gp53 bind about 84% of circulating antibodies on day 80 post‐infection, this percentage was only 38% in Swiss CD‐1 mice. These data on the antigenicity of gp53 contrast with data forTrichinellaCLE antigens, in that most circulating antibodies reactive with CLE antigens recognized tyvelose‐containing epitopes (57% and 58% of circulating antibodies in BALB/c and Swiss CD‐1 mice, respectively). Together these results demonstrate that gp53 is recognized during infection but is antigenically different from otherTrichinellaTSL‐1 antigens.
Serum IgG3 to the Plasmodium falciparum merozoite surface protein 2 is strongly associated with a reduced prospective risk of malaria
Authors: Metzger Wolfram G. , Okenu Daniel M. N. , Cavanagh David R. , Robinson Jane V. , Bojang Kalifa A. , Weiss Helen A. , McBride Jana S. , Greenwood Brian M. , Conway David J.
Published: September 2003

The merozoite surface protein 2 (MSP2) of Plasmodium falciparum is recognized by human antibodies elicited during natural infections, and may be a target of protective immunity. In this prospective study, serum IgG antibodies to MSP2 were determined in a cohort of 329 Gambian children immediately before the annual malaria transmission season, and the incidence of clinical malaria in the following 5 months was monitored. Three recombinant MSP2 antigens were used, representing each of the two major allelic serogroups and a conserved region. The prevalence of serum IgG to each antigen correlated positively with age and with the presence of parasitaemia at the time of sampling. These antibodies were associated with a reduced subsequent incidence of clinical malaria during the follow‐up. This trend was seen for both IgG1 and IgG3, although the statistical significance was greater for IgG3, the most common subclass against MSP2. After adjusting for potentially confounding effects of age and pre‐season parasitaemia, IgG3 reactivities against each of the major serogroups of MSP2 remained significantly associated with a lower prospective risk of clinical malaria. Individuals who had IgG3 reactivity to both of the MSP2 serogroup antigens had an even more significantly reduced risk. Importantly, this effect remained significant after adjusting for a simultaneous strong protective association of antibodies to another antigen (MSP1 block 2) which itself remained highly significant.
Metalloendopeptidases from the intestinal brush border of Haemonchus contortus as protective antigens for sheep
Authors: Smith W. D. , Newlands G. F. J. , Smith S. K. , Pettit D. , Skuce P. J.
Published: September 2003

Substantial protection against the economically important nematode Haemonchus contortus has been achieved by immunizing sheep with a glycoprotein fraction isolated from the intestinal membranes of this parasite. This fraction has been termed Haemonchus galactose‐containing glycoprotein complex (H‐gal‐GP) since it was originally isolated through its selective binding to lectins with a specificity for N‐acetylgalactosamine. A major component of this highly protective antigen complex is a family of four zinc metalloendopeptidases, designated MEPs 1–4. Various combinations of these MEPs were evaluated in immunization–challenge trials in sheep. In two experiments a combination of all four MEPs, separated from the rest of the complex by gel filtration in 8 m urea, significantly reduced H. contortus egg counts by 45 and 50%, an effect not significantly different from that conferred by 8 m urea treatment of H‐gal‐GP itself. Similarly, MEP3 alone or MEPs 1, 2 and 4 in combination, electroeluted from the complex following SDS gel electrophoresis, each reduced egg counts by some 33%. The MEPs are therefore protective components of H‐gal‐GP and from previously published findings, it appears that MEP3 is the most effective member of this metalloendopeptidase family. However, there was no significant protection when sheep were immunized with fully reduced and denatured H‐gal‐GP or with bacterially expressed recombinant forms of MEP 1 or the principal domains of MEP3, suggesting that conformational epitopes on the MEPs are required for immunity.
Regulatory effects of IL‐12 and IL‐18 on Onchocerca volvulus‐ and Entamoeba histolytica‐specific cellular reactivity and cytokine profiles
Authors: Pfaff Alexander W. , Kirch Astrid K. , Hoffmann Wolfgang H. , Banla Meba , Schulz‐Key Hartwig , Geiger Stefan M. , Soboslay Peter T.
Published: September 2003

In the present study, the cytokines interleukin (IL)‐12 and IL‐18 were evaluated for their capacity to modulate and to re‐direct in vitro parasite antigen‐specific cellular responsiveness in patients exposed to Onchocerca volvulus and Entamoeba histolytica infection. We found that IL‐18 was highly capable of reducing parasite antigen‐induced IL‐10 production by PBMC. In contrast, addition or neutralization of IL‐12, also in combination with IL‐18 and the interferon‐γ‐inducible chemokine IP‐10 did not affect IL‐10 production. Interestingly, the highest IL‐10 levels were measured when IL‐18 and IP‐10 were both neutralized. Although having no effect on IL‐10, IL‐12 strongly promoted spontaneous and parasite antigen‐driven IFN‐γ production by PBMC, whereas IL‐18 was only moderately affecting IFN‐γ release by PBMC re‐stimulated with E. histolytica‐ or O. volvulus‐specific antigens. Both IL‐12 and IL‐18 diminished the cellular production of IL‐13, and a synergistic effect was observed when the cytokines were combined. Likewise, neutralization of IL‐12 enhanced Entamoeba and Onchocerca antigen‐driven IL‐13 production, but no further increase of IL‐13 was observed, when anti‐IL‐12 and anti‐IL‐18 were used together. This study disclosed that IL‐18 will significantly down‐regulate parasite‐specific IL‐10 production, whereas IL‐12 induced IFN‐γ and inhibited IL‐13 production by PBMC from humans exposed to O. volvulus and E. histolytica. Such selective immune‐regulatory capacity of IL‐12 and IL‐18 may comprise an important tool to re‐direct polarized cytokine responses towards a balanced Th1/Th2 cytokine profile, which may prevent pathology and promote immunity against helminth and protozoan parasite infections.