bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐10 expressed at early tumour sites induces subsequent generation of CD4+ T‐regulatory cells and systemic collapse of antitumour immunity
Authors: Seo Naohiro , Hayakawa Satoshi , Takigawa Masahiro , Tokura Yoshiki 
Published: March 2003

SummaryWe investigated the relationship between transforming growth factor‐β (TGF‐β)‐secreting T‐regulatory (Tr) cells and anti‐B16 melanoma immunity, and studied the association of early cytokines expressed at tumour sites with the generation of Tr cells. A large number of CD4+ Tr cells producing interleukin (IL)‐4, IL‐10 and TGF‐β accumulated with functionally depressed CD8+ cytotoxic T lymphocytes (CTLs) at tumour sites on day 20 after subcutaneous (s.c.) inoculation of B16 tumour cells. Tr cells consisted of two populations, which were termed T helper 3 (Th3) and Tr1 cells. B16‐infiltrating Tr cells strongly inhibited the generation of B16‐specific T helper 1 (Th1) cells in a TGF‐β‐dependent manner and were assumed to suppress effective generation of CTLs. In addition, B16 cells markedly progressed in mice transferred adoptively by the cultured B16‐infiltrating Tr cells compared with untreated mice. The capacity of these Tr cells to produce TGF‐β was hampered by neutralizing anti‐IL‐10 and partly anti‐IL‐4 monoclonal antibodies (mAbs) injected intralesionally during the early development of B16 tumours, and this treatment markedly attenuated B16 growth. Furthermore, a lesional injection of recombinant mouse IL‐10 at an early tumour site resulted in the vigorous progression of B16 tumours. These results provide evidence that Tr cells, belonging to the T helper 3/T‐regulatory 1 (Th3/Tr1) type, are activated in B16‐bearing hosts under the influence of T helper 2 (Th2) cytokines, mainly IL‐10 (produced at early tumour lesions), and that this regulatory T‐cell population functions as a suppressor of anti‐B16 immunity.
In vitro stimulation with a non‐peptidic alkylphosphate expands cells expressing Vγ2‐Jγ1.2/Vδ2 T‐cell receptors
Authors: Evans Peter S. , Enders Patrick J. , Yin Cheng , Ruckwardt Tracy J. , Malkovsky Marek , Pauza C. David 
Published: March 2003

SummaryThe majority of peripheral blood γδ T cells in healthy adult humans express the Vγ2/Vδ2 T‐cell receptor (TCR) and generate TCR‐mediated, major histocompatibility complex (MHC)‐unrestricted proliferative responses to low molecular weight alkylphosphates. Vγ2/Vδ2 populations after antigen proliferation maintained diversity in the CDR3s of Vγ2 mRNA, indicating that the response was polyclonal or oligoclonal, and were enriched for Vγ2 TCR chains containing the Jγ1.2 segment. Alkylphosphate stimulation further skewed an already biased peripheral blood γδ T‐cell population and increased the abundance of Vγ2‐Jγ1.2/Vδ2 T cell receptors, suggesting similarities between the alkylphosphate response and peripheral selection mechanisms shaping this repertoire in human beings.
Schiff base‐mediated co‐stimulation primes the T‐cell‐receptor‐dependent calcium signalling pathway in CD4 T cells
Authors: Hall Simon R. , Rhodes John 
Published: March 2003

SummaryIn addition to macromolecular interactions that provide co‐stimulation during antigen‐presenting cell (APC) and CD4+ T‐cell conjugation, covalent chemical events between specialized ligands have been implicated in T‐cell co‐stimulation. These take the form of transient Schiff base formation between carbonyls and amines expressed on APC and T‐cell surfaces. Small Schiff base‐forming molecules, such as tucaresol, can substitute for the physiological donor of carbonyl groups and provide co‐stimulation to T cells, thereby functioning as orally active immunopotentiatory drugs. The Schiff base co‐stimulatory pathway in T cells has been partially characterized in terms of changes in Na+ and K+ transport, and activation of the mitogen activated protein kinase (MAPK) ERK2. In the present study, the effects of Schiff base co‐stimulation by tucaresol on the T‐cell receptor (TCR)‐dependent pathway leading to Ca2+ release were investigated. Schiff base co‐stimulation by tucaresol was found to prime for enhanced TCR‐dependent phospholipase C‐γ phosphorylation, inositol 1,4,5‐triphosphate production, and Ca2+ mobilization that correlated with functional enhancement of interleukin‐2 production in primary T cells. The effects on Ca2+ occurred comparably in Jurkat and primary CD4+ T cells responding to anti‐CD3 monoclonal antibody. Enhancement of the Ca2+ response required a 10‐min priming period and was prevented by prior covalent ligation of cell‐surface free amino groups by sulpho‐N‐hydroxy succinimido‐biotin; clofilium‐mediated inhibition of tucaresol‐induced changes in intracellular K+; and selective inhibition of the MAPK pathway. The data are consistent with a priming mechanism in which late co‐stimulation‐triggered events exert a positive influence on early TCR‐triggered events. In additional studies of murine T cells expressing trans‐gene TCRs, tucaresol was likewise shown to prime for enhanced Ca2+ mobilization in response to physiological TCR‐engagement by MHC–peptide complexes.
Administration of plasmids expressing interleukin‐4 and interleukin‐10 causes BALB/c mice to induce a T helper 2‐type response despite the expected T helper 1‐type response with a low‐dose infection ofLeishmania major
Authors: Yamakami Kazuo , Akao Shinkichi , Tadakuma Takushi , Nitta Yoshio , Miyazaki Jyun‐Ichi , Yoshizawa Nobuyuki 
Published: March 2003

SummaryBALB/c mice are susceptible to developing an infection with Leishmania major as a result of a fatal T helper 2 (Th2)‐type response. However, mice infected with a low dose of parasites are reported to be able to overcome the lesions associated with a T helper 1 (Th1)‐type response. To clarify why a difference in the dose of parasites induces a difference in the polarization of the Th phenotype, we first attempted to measure cytokine production. Soon after infection, the mice given high doses of parasites produced elevated levels of both Th1 [interferon‐γ (IFN‐γ)] and Th2 [interleukin (IL)‐4 and IL‐10] cytokines. However, when assessed at 1 and 2 weeks after infection, no significant difference in the balance of Th1 and Th2 cytokines could be detected between mice infected with low or high doses of L. major. These results support the notion that the Th2 cytokine levels at an early phase of infection could be a key factor for the induction of a Th2 response. In order to assess the efficacy of Th2 cytokines, the mice infected with low doses of L. major were co‐administered IL‐4 plasmid and IL‐10 plasmid. Consequently, the mice (which originally exhibited a Th1 response) showed progressive disease and developed a Th2 response. However, administration of these plasmids at 7 days postinfection could not alter the Th polarization. Furthermore, production of IL‐12 from the spleen cells stimulated by L. major was suppressed in the presence of IL‐4 and IL‐10. These results strongly suggest that the susceptibility to L. major in BALB/c mice depends on the persistence of Th2 cytokine levels at an early phase of infection.
T‐cell activation occurs simultaneously in local and peripheral lymphoid tissue following oral administration of a range of doses of immunogenic or tolerogenic antigen although tolerized T cells display a defect in cell division
Authors: Smith Karen M. , Davidson Joanne M. , Garside Paul 
Published: March 2003

SummaryHow the mucosal immune system promotes active immunity against harmful organisms but tolerance to commensal bacteria or dietary antigens is poorly understood. Thus, the antigen‐presenting cell (APC), site of antigen presentation, and effector mechanisms responsible for oral priming and tolerance remain unclear. Characterizing differences between oral priming and tolerance may improve the exploitation of oral tolerance for therapeutic applications and aid the design of oral vaccines. To address these questions we compared the mucosal and systemic activation and localization of antigen‐specific T cells during the induction of oral priming and tolerance. Activation marker expression and cell division by tg T cells was determined in conjunction with their anatomical location. These studies show that after feeding, T cells are activated in both peripheral and local lymphoid tissues within 6 hr, irrespective of the presence of adjuvant. Subsequently, T‐cell accumulation can be detected simultaneously in peripheral and mesenteric lymph nodes and Peyer's patches within 24 hr of feeding, but only after 3 days post feeding in the lamina propria. Primed and tolerized T cells adopted similar phenotypes as assessed by activation marker expression. However, within the mesenteric lymph nodes (MLN) tolerized T cells underwent significantly fewer divisions than primed T cells. Thus, T‐cell activation and expansion occurs throughout the animal after feeding a range of doses of antigen, irrespective of whether priming or tolerance is the eventual outcome. However, the presence of an adjuvant enhances clonal expansion in the MLN while tolerized T cells display defective cell division.
Hydroquinone, a reactive metabolite of benzene, enhances interleukin‐4 production in CD4+ T cells and increases immunoglobulin E levels in antigen‐primed mice
Authors: Lee M. H. , Chung S. W. , Kang B. Y. , Kim K.‐M. , Kim T. S. 
Published: March 2003

SummaryExposure to cigarette smoke is known to increase the risk of the development of allergic disease. The mechanism is not well understood. In this study, we determined the effect of hydroquinone (HQ), a major metabolite of benzene present in large quantities in cigarette tar, on interleukin‐4 (IL‐4) production by CD4+ T cells. HQ significantly enhanced IL‐4 production by keyhole limpet haemocyanin (KLH)‐primed CD4+ T cells in a dose‐dependent manner. The enhancing effect of HQ on IL‐4 production was maximal at a concentration of 50 µm. It increased the level of IL‐4 production approximately 10‐fold. HQ enhanced IL‐4 mRNA expression and also IL‐4 gene promoter activity, suggesting that the enhancing effect of HQ on IL‐4 production may occur at the transcriptional level. Furthermore, the injection of KLH‐primed mice with HQ resulted in a significant increase in the levels of IL‐4 and immunoglobulin E. These findings provide evidence that HQ, a major component of cigarette tar, may enhance allergic immune responses by inducing the production of IL‐4 in CD4+ T cells.
Mistletoe lectins enhance immune responses to intranasally co‐administered herpes simplex virus glycoprotein D2
Authors: Lavelle E. C. , Grant G. , Pusztai A. , Pfüller U. , Leavy O. , McNeela E. , Mills K. H. G. , O'Hagan D. T. 
Published: March 2003

SummaryThe mucosal adjuvant properties of the three type 2 ribosome‐inactivating proteins (RIPs) from the European mistletoe, Viscum album L., were investigated. Mistletoe lectins were compared with cholera toxin (CT) as adjuvants when delivered nasotracheally together with herpes simplex virus glycoprotein D2 (gD2). All three mistletoe lectins (MLI, MLII, MLIII) were potent mucosal adjuvants. Co‐administration of MLI, MLII or MLIII with gD2 led to significantly higher levels of gD2‐specific mucosal immunoglobulin A (IgA) and systemic immunoglobulin G (IgG) antibody than when the antigen was delivered alone. The levels of antibodies induced were similar to those generated in mice immunized with gD2 and the potent mucosal adjuvant CT. Administration of ML1 with gD2 enhanced the antigen‐specific splenic T‐cell proliferative response. Interleukin‐5 (IL‐5), but not interferon‐γ (IFN‐γ), was detected in supernatants from splenocytes stimulated in vitro with gD2. This indicates that MLI enhanced type 2 T‐helper cell (Th2) responses to the bystander antigen, gD2. Analysis of the gD2‐ and lectin‐specific IgG subclass titres in mice immunized with gD2 and MLI, MLII or MLIII revealed a high ratio of IgG1 : IgG2a, which is compatible with the selective induction of Th2‐type immune responses.
Generation and characterization of ovine dendritic cells derived from peripheral blood monocytes
Authors: Chan Simon S. M. , Mcconnell Ian , Blacklaws Barbara A. 
Published: March 2003

SummaryDendritic cells (DCs) are professional antigen‐presenting cells with a highly immunostimulatory function and the capacity to activate naïve T cells. In recent years the rapid progress in mouse and human DC research can be mainly attributed to the generation of DCs from precursor cells in vitro, although a lack of reagents has hampered DC research in many large animal models. Here we describe the generation and characterization of ovine monocyte‐derived DCs in vitro. In addition to the characteristic morphology and non‐adherence of DCs, peripheral blood mononuclear cell monocytes cultured with ovine granulocyte–macrophage colony‐stimulating factor (GM–CSF) and interleukin‐4 (IL‐4) expressed CD11c and major histocompatibility complex (MHC) class II, but did not express CD14. High levels of endocytosis and an ability to stimulate antigen‐specific proliferation of CD4 T lymphocytes were also demonstrated.
Down‐regulation of the myeloid homeobox protein Hex is essential for normal T‐cell development
Authors: Mack David L. , Leibowitz David S. , Cooper Scott , Ramsey Heather , Broxmeyer Hal E. , Hromas Robert 
Published: March 2003

SummaryThe haematopoietic homeobox gene Hex (also called Prh) is expressed in myeloid cells and B cells but not T cells. To investigate whether Hex levels might play a role in myeloid versus T‐cell development, two types of transgenic mouse lines were constructed, each with ectopic expression of Hex in T cells (CD11a/Hex and Lck/Hex). Both these types of transgenic mouse had the same defects in T‐cell maturation, indicating that proper T‐cell development may be dependent not just on the up‐regulation of lymphoid‐specific transcriptional regulators but also on the co‐ordinated down‐regulation of myeloid‐specific transcriptional regulators such as Hex. In addition, Hex over‐expression significantly increased myeloid progenitor cycling, which may explain its role in retrovirally induced murine leukaemia.
Carbohydrate‐based particles: a new adjuvant for allergen‐specific immunotherapy
Authors: Grönlund Hans , Vrtala Susanne , Wiedermann Ursula , Dekan Gerhard , Kraft Dietrich , Valenta Rudolf , Van Hage‐Hamsten Marianne 
Published: March 2003

SummaryThe occurrence of systemic anaphylactic side‐effects in the course of allergen‐specific immunotherapy has been strongly reduced by the adsorption of allergens to aluminium hydroxide, the most frequently used adjuvant in humans. Using the major timothy grass pollen allergen, Phl p 5b, in its recombinant form for immunization of mice, we demonstrate that carbohydrate‐based particles (CBP) exhibit several potential advantages over aluminium‐hydroxide as adjuvant for immunotherapy. Similar to alum‐bound rPhl p 5b, CBP‐bound rPhl p 5b induced a stronger antibody and cytokine response than unbound rPhl p 5b after subcutaneous injection in mice. The antibodies induced by CBP‐bound rPhl p 5b, exhibited potentially beneficial activities as they cross‐reacted with group 5 allergens from five other grass species and inhibited the binding of grass pollen allergic patients IgE to Phl p 5b. Alum‐bound rPhl p 5b induced a preferential allergen‐specific Th2‐response characterized by high immunoglobulin G1 (IgG1) antibody levels and elevated interleukin (IL)‐4 and IL‐5 production in cultured splenocytes. By contrast, CBP‐bound rPhl p 5b, but not rPhl p 5b alone or coadministered with CBP, induced a mixed allergen‐specific T helper 1 (Th1)/Th2 immune response characterized by the additional production of allergen‐specific IgG2a/b antibody responses and elevated interferon‐γ production. Conjugation of rPhl p 5b to CBP yielded a stable vaccine formulation with preserved immunogenic features of the allergen and, in contrast to alum, induced no granulomatous tissue reactions. Based on these results, CBP is suggested as a potentially useful adjuvant for specific immunotherapy of IgE‐mediated allergies.
Identification of a new cluster of T‐cell receptor delta recombining elements
Authors: Przybylski Grzegorz K. , Wanzeck Jens , Verschuren Martie C. M. , Van Dongen Jacques J. M. , Serke Stephan , Schmidt Christian A. 
Published: March 2003

SummaryWithin the human T‐cell receptor δ (TCRD) gene we have identified a new cluster of seven δ recombining elements (δRec2.1–2.7), located 2·6–5·2 kilobases downstream of the Vδ2 gene segment. The δRec2 elements are isolated recombining signal sequences (RSS), which were shown to rearrange with the Dδ3 and Jδ1 segments of the TCRD gene as well as with the ψJα of the TCRA gene. Rearrangements involving the δRec2 elements were found in all peripheral blood (PB) samples from 10 healthy individuals, although their frequency was about 100‐fold lower than that of classical δRec rearrangements. The total frequency of δRec2 rearrangements was lower in PB T lymphocytes, as compared with thymocytes, suggesting that they are deleted during T‐cell development. The decrease of the frequency of the δRec2‐Dδ3 rearrangements was most prominent: 11 times lower in PB T lymphocytes than in thymocytes. Since the δRec2‐Jδ1 rearrangements contained the Dδ3 segment in the junctional region, we assume that they are derived from the δRec2‐Dδ3 rearrangements. In contrast, the majority of δRec2‐ψJα rearrangements did not contain the Dδ3 segment, indicating that they are single step rearrangements. The δRec2‐Jδ1 and δRec2‐ψJα rearrangements seem to be T‐lineage specific, but the δRec2‐Dδ3 rearrangements were also found at very low frequencies in B lymphocytes and natural killer cells. Our results suggest that δRec2 rearrangements are transient steps in the recombinatorial process of the TCRAD locus and are probably deleted by subsequent Vα‐Jα rearrangements. We hypothesize, that in a similar manner to the classical δRec rearrangements, the δRec2 rearrangements might also contribute to T‐cell differentiation towards the TCR‐αβ lineage.
IT outsourcing: frameworks for conceptualizing practice and perception
Authors: Hancox Martin , Hackney Ray 
Published: March 2003

Abstract.This paper seeks to conceptualize theory and practice of information technology (IT)‐based outsourcing. It uses four conceptual frameworks in this respect – core competencies, transaction cost economics, agency theory and partnership – in an empirical comparison of IT outsourcing in the public and private sectors within the UK. The qualitative research methodology involved interviews with IT managers in both sectors and documentary analysis of outsourcing vendors’ literature. The findings suggest that practices and perceptions of IT outsourcing found in the two sectors support the basic principles of some frameworks more than others, e.g. core competencies, transaction cost economics and agency theory are well developed with partnerships less so. However, using all four frameworks improves understanding of multifaceted strategic practice in fundamentally different types of organization and helps to expose some issues which have not emerged in previous outsourcing studies.
Structure and expression of tandemly duplicated xanthine dehydrogenase genes of the silkworm (Bombyx mori)
Authors: Kômoto N. , Yukuhiro K. , Tamura T. 
Published: March 2003

AbstractXanthine dehydrogenase (XDH) is a molybdoenzyme which catalyses oxidation of xanthine and hypoxanthine to uric acid. We isolated genomic clones of silkworm (Bombyx mori) XDH genes (BmXDH1 and BmXDH2). The BmXDH2 The BmXDH2 gene is located upstream from the BmXDH1 gene and they show a tandemly duplicated structure. Both BmXDH genes were expressed in the fat body and Malpighian tubules, whereas only the BmXDH1 gene was expressed in the midgut. Phylogenetic analysis indicates that BmXDH gene duplication occurred after the divergence of the silkworm and dipteran species. Intron insertion site comparison shows that some introns were lost during insect XDH gene evolution.
Cloning of an aquaporin‐like cDNA and in situ hybridization in adults of the mosquito Aedes aegypti (Diptera: Culicidae)
Authors: Pietrantonio P. V. , Jagge C. , Keeley L. L. , Ross L. S. 
Published: March 2003

AbstractA cDNA encoding a putative water channel protein, aquaporin, was cloned from a cDNA library of Aedes aegypti Malpighian tubules. The cDNA encodes a 26.11 kDa protein similar to insect aquaporins from Haematobia irritans exigua (Diptera) and Cicadella viridis (Homoptera), and to mammalian aquaporin 4. Localization of the messenger RNA (mRNA) was performed by in situ hybridization of Malpighian tubules and analysed by fluorescence and confocal microscopy. The mRNA was localized in tracheolar cells associated with the Malpighian tubules. No signal was detected in the Malpighian tubule epithelium. The molecular mechanisms for water movement between tissues and tracheoles are not yet elucidated in insects. Our results suggest a model to explain fluid movements in tracheoles during insect respiration.
The tetraspanin superfamily in insects
Authors: Todres E. , Nardi J. B. , Robertson H. M. 
Published: March 2003

AbstractWe describe four members of the tetraspanin/TM4SF superfamily of proteins that were identified in expressed sequence tag projects on the antennae of Manduca sexta moths and Apis mellifera honey bees. The three moth genes are expressed in the sensillar epithelium of male antennae, and some are expressed in female antennae, haemocytes, wing scale cell primordia and/or embryonic tissues. These proteins are probably involved in diverse cellular processes, much like their vertebrate homologues. A phylogenetic analysis of all known tetraspanins, including thirty‐seven members of the superfamily revealed by the Drosophilamelanogaster genome and twenty in the nematode Caenorhabditiselegans genome, reveals some phylum‐specific gene amplification, in particular a contiguous array of eighteen genes in the D. melanogaster genome.
Sequence, secondary structure and phylogenetic analyses of the ribosomal internal transcribed spacer 2 (ITS2) in the Timarcha leaf beetles (Coleoptera: Chrysomelidae)
Authors: Gómez‐Zurita J. , Juan C. , Petitpierre E. 
Published: March 2003

AbstractInternal transcribed spacer 2 (ITS2) sequences of the nuclear rDNA in forty‐seven specimens (thirty‐four species) of the leaf beetle genus Timarcha have been studied. Timarcha ITS2 (523 bp on average) share some sequence features with other Chrysomeloidea relatives (Chrysolina, Diabrotica and Bruchus) but have no clear similarity with any other arthropod ITS2 sequences. Interspecific divergences are in the range 0.002–0.166, and 0.124–0.206 in the comparisons between subgenera. No evidence of intragenomic divergent ITS2 sequences has been found. Secondary structures are concordant with the four‐domain model proposed for vertebrates and yeast, but differs from those proposed for dipterans. Phylogenetic analysis of the ITS2 data confirms the results of a previous study based on mitochondrial sequences, as the basality of the Metallotimarcha subgenus and the absence of phylogenetic support for the Timarchostoma subgenus.
Molecular characterization of ribosomal DNA polymorphisms discriminating among chromosomal forms of Anopheles gambiae s.s.
Authors: Favia G. , Lanfrancotti A. , Spanos L. , Sidén‐Kiamos I. , Louis C. 
Published: March 2003

AbstractThe sequence of a 2.3 kb long DNA segment derived from the 5′‐most end of the ribosomal intergenic spacer was determined in three chromosomal forms of Anopheles gambiae s.s. The analysis revealed that the sequence of the Mopti form differed from that of the Bamako and Savanna forms by a total of ten nucleotide substitutions. Using these sequence variations we set up a diagnostic polymerase chain reaction (PCR) assay to distinguish mosquitoes belonging to the three chromosomal forms, facilitating studies on the distribution and the ecology of these incipient taxa. The assay also allows to distinguish whether a given specimen could represent a heterozygote between Mopti and Savanna or Bamako.