bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen‐induced arthritis
Authors: Doncarli Alexandra , Stasiuk Lisa M. , Fournier Catherine , Abehsira‐Amar Orly 
Published: March 2007

AbstractOver the past decade, the central role of T cells in the process of collagen‐induced arthritis (CIA) has been extensively documented. The inflammatory features of CIA and its successful modulation after treatment in vivo with Th2 lymphokines, known to down‐regulate proinflammatory cytokines, classify CIA as a Th1‐mediated disease. However, no direct evidence for the presence of the different T helper subsets has been obtained. To identify the collagen‐specific CD4+ T cell subset(s) developing during the course of CIA, lymph nodes from susceptible DBA/1 mice (H‐2q) were harvested at different times after injection of bovine type II collagen in Freund's complete adjuvant and checked by enzyme‐linked immunospot assay for the production of interferon (IFN)‐γ and interleukin (IL)‐4. The results clearly showed that type II collagen‐specific T cells secreting either IFN‐γ, IL‐4, or both, develop early in vivo, before the onset of arthritis: the number of IFN‐γ‐secreting cells was already maximal 15 days after immunization, whereas more IL‐4‐secreting cells were found at day 30, just before the onset of clinical arthritis. Another strategy was to establish collagen‐specific CD4+ T cell lines and sublines in vitro and to analyze their lymphokine secretion pattern. Lines generated 8 days after immunization displayed a mixed lymphokine secretion pattern characteristic of Th0 cells or of a mixture of Th1 and Th2 cells. After limiting dilution of a day 8 line, 60% of the growing sublines were Th0‐like (secreting IFN‐γ, IL‐4, and IL‐5), and 25% were Th1 (secreting IFN‐γ). By day 25 post‐immunization, 33% of the generated sublines were Th0‐like, 11% Th1, and 56% Th2 (secreting IL‐4 and IL‐5). Moreover, all the sublines raised from the lymph nodes of arthritic mice harvested at day 55 secreted high amounts of Th2 lymphokines, and only 3 out of 14 also produced some IFN‐γ. This study demonstrates that during the course of CIA the collagen‐specific CD4+ T cell response shifts in vivo from a dominant Th0/Th1 response to a clear Th2 phenotype. These results contribute to our understanding of the collagen‐specific CD4+ T helper subsets which develop during the induction and clinical phases of CIA.
The defined attenuated Listeria monocytogenes Δmpl2 mutant is an effective oral vaccine carrier to trigger a long‐lasting immune response against a mouse fibrosarcoma
Authors: Paglia Paola , Arioli Ivano , Frahm Nicole , Chakraborty Trinad , Colombo Mario P. , Guzmàn Carlos A. 
Published: March 2007

AbstractListeria monocytogenes has been proposed as a carrier to elicit major histocompatibility complex class‐I restricted immune responses able to protect against tumor challenge. In this study the properties of the attenuated L. monocytogenes Δmpl2 mutant has been evaluated in vivo against a highly aggressive mouse fibrosarcoma which expresses β‐galactosidase (β‐gal) as a tumor‐associated antigen (TAA). Immunization with the vaccine prototypes resulted in both elicitation of specific antibodies and generation of cytotoxic lymphocytes (CTL). Oral vaccination protected 55–64% of the immunized animals from tumor take (p < 0.01) and strongly reduced the average size of the tumor in the other 34–45% (p < 0.01). Vaccinated mice developed a long‐lasting response, which resulted in 100% protection from a subsequent tumor challenge. Substitution of the whole TAA by its CTL‐defined immunodominant epitope resulted in 43% protection, suggesting a contribution of the humoral response to the observed antitumor effect. No statistically significant differences were observed in the antitumor response when mice were immunized with strains expressing the immunodominant TAA epitope in the context of carrier proteins which were either exported or restricted to the bacterial cytoplasm. This suggests that the topology of the recombinant antigen does not play a major role in the outcome of the protective response.
The chemokine SDF‐1, stromal cell‐derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4
Authors: D'Apuzzo Massimo , Rolink Antonius , Loetscher Marcel , Hoxie James A. , Clark‐Lewis Ian , Melchers Fritz , Baggiolini Marco , Moser Bernhard 
Published: March 2007

AbstractIn the bone marrow, progenitor (pro‐) and precursor (pre‐) B cells depend on close contact with stromal cells for growth and maturation. Stromal cell‐derived factor 1 (SDF‐1), also known as pre‐B cell growth‐stimulating factor, is produced by bone marrow stromal cells and was reported to act together with interleukin‐7 as co‐mitogen for pre‐B cells. SDF‐1 was recently shown to be a chemokine which is chemotactic for different types of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220+ bone marrow cells and several B cell lines characteristic for different stages of B lymphopoiesis, we now show that SDF‐1 is a potent attractant for pro‐ and pre‐B cells, but is inactive on B cells at later stages of development. In early B cell precursors, SDF‐1 induced intracellular Ca2+ mobilization and in vitro migration with a potency and efficacy similar to that observed for chemokines acting on blood leukocytes. These responses were mediated via CXCR4 as they could be inhibited by an anti‐receptor antibody. SDF‐1 is the first chemokine shown to act on early‐stage B cell precursors. Mice lacking SDF‐1 die perinatally and show a severe deficiency in B lymphopoiesis. We propose that SDF‐1 released from the stromal cells exerts its critical hematopoietic function by selectively attracting and confining early B cell precursors within the bone marrow microenvironment that provides the necessary factors for growth and differentiation.
Src family‐selective tyrosine kinase inhibitor, PP1, inhibits both FcεRI‐ and Thy‐1‐mediated activation of rat basophilic leukemia cells
Authors: Amoui Mehran , Dráber Petr , Dráberová Lubica 
Published: March 2007

AbstractCross‐linking of the surface receptor with high affinity for IgE (FcεRI) by multivalent antigen/immunoglobulin E complexes, as well as aggregation of Thy‐1 glycoprotein by monoclonal antibodies lead in rat basophilic leukemia cells, clone RBL‐2H3, to tyrosine phosphorylation of several cellular proteins, followed by a release of secretory components. To investigate the molecular mechanisms of FcεRI‐ and Thy‐1‐mediated transmembrane signaling and to map a step at which they converge into a common secretory pathway, we used a novel Src family‐selective tyrosine kinase inhibitory, 4‐amino‐5‐(4‐methylphenyl)‐7‐(t‐butyl)pyrazolo[3,4‐d]pyrimidine (PP1), and analyzed its inhibitory activity on cell activation. Here we show that in RBL‐2H3 cells PP1 demonstrates substrate specificity for a Src family kinase Lyn. In immunocomplex kinase assays in vitro, PP1 inhibited the Lyn kinase activity at nanomolar levels without any effect on Syk kinase activity. However, in RBL cells activated via aggregation of FcεRI, phosphorylation of both Syk and Lyn kinases was inhibited. FcεRI‐ and Thy‐1‐mediated early (protein‐tyrosine phosphorylation) and late (release of β‐hexosaminidase) activation events were similarly affected by PP1. The inhibition was specific for membrane receptor‐mediated signaling and was not observed in cells activated by an exposure to pervanadate. The combined data suggest that activation of Lyn is the early activation step at which the FcεRI‐ and Thy‐1‐mediated activation pathways of mast cells and basophils may converge.
Differential T cell receptor‐mediated signaling in naive and memory CD4 T cells
Authors: Farber Donna L. , Acuto Oreste , Bottomly Kim 
Published: March 2007

AbstractNaive and memory CD4 T cells differ in cell surface phenotype, function, activation requirements, and modes of regulation. To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression. Naive CD4 T cells signal through TCR/CD3 similar to unseparated CD4 T cells, producing multiple tyrosine‐phosphorylated protein species overall and phosphorylating the T cell‐specific ZAP‐70 tyrosine kinase which is recruited to the CD3ζ subunit of the TCR. Memory CD4 T cells, however, exhibit a unique pattern of signaling through TCR/CD3. Following stimulation through TCR/CD3, memory CD4 T cells produce fewer species of tyrosine‐phosphorylated substrates and fail to phosphorylate ZAP‐70, yet unphosphorylated ZAP‐70 can associate with the TCR/CD3 complex. Moreover, a 26/28‐kDa phosphorylated doublet is associated with CD3ζ in resting and activated memory but not in naive CD4 T cells. Despite these differences in the phosphorylation of ZAP‐70 and CD3‐associated proteins, the ZAP‐70‐related kinase, p72syk, exhibits similar phosphorylation in naive and memory T cell subsets, suggesting that this kinase could function in place of ZAP‐70 in memory CD4T cells. These results indicate that proximal signals are differentially coupled to the TCR in naive versus memory CD4 T cells, potentially leading to distinct downstream signaling events and ultimately to the diverse functions elicited by these two CD4 T cell subsets.
In vitro responses of human CD45R0brightRA− and CD45R0−RAbright T cell subsets and their relationship to memory and naive T cells
Authors: Young Joyce L. , Ramage Judith M. , Gaston J. S. Hill , Beverley Peter C. L. 
Published: March 2007

AbstractThe cellular basis of immunological memory, particularly with respect to T cells is not understood. In humans, monoclonal antibodies to CD45 have been used to identify memory (CD45R0) and naive (CD45RA) T cells. However, this identification has been called into question by various studies which suggest that high molecular weight CD45 isoforms may be re‐expressed by previously activated cells. In the present study, using cultures which supported responses of naive T cells, we examined the responses of purified CD45R0brightRA− or CD45R0−‐RAbright T cell subsets. The former subset was found to respond preferentially to recall antigens with minimal responses apparent to neo‐(or non‐recall)‐antigens. The inverse pattern was found for CD45R0−RAbright T cells, which converted to CD45R0brightRA− after stimulation with a neo‐antigen. Moreover, the two populations of T cells exhibited distinct response kinetics with a faster response evident from the CD45R0brightRA−T cells compared to the CD45R0−RAbright subset. The poor responses of CD45R0−RAbright T cells to recall antigens compared to neo‐antigens suggests that this putative naive population is specifically depleted of reactive T cells following an encounter with antigen. We propose that T cell priming results in the stimulation of many CD45R0−RAbright T cells with various T cell receptor specificities from which memory T cells are selected for survival. If re‐expression of higher molecular weight isoforms does occur in humans in vivo, our results suggest that R0 expression would be retained (CD45R0+RA+). Alternatively, if primed CD45R0−RAbright T cells exist, they are not prevalent in peripheral blood and thus may be sequestered within lymphoid tissues. Our data support the view that in human peripheral blood, CD45R0bright and CD45RAbright expression identify memory and naive CD4+ T cells, respectively.
Crucial role of marginal zone macrophages and marginal zone metallophils in the clearance of lymphocytic choriomeningitis virus infection
Authors: Seiler Peter , Aichele Peter , Odermatt Bernhard , Hengartner Hans , Zinkernagel Rolf M. , Schwendener Reto A. 
Published: March 2007

AbstractMacrophages play a key role in the immune defense against pathogens. They control early invasion by antigen‐unspecific phagocytosis of pathogens and act as professional antigen‐presenting cells to induce antigen‐specific T cell responses. To investigate the involvement of particular subsets of the splenic macrophages in an antiviral immune response, we selectively depleted mice of splenic marginal zone macrophages (MZM) and marginal zone metallophils (MM) using the clodronate liposome depletion technique. MZM‐ and MM‐depleted mice were not able to control an infection with lymphocytic choriomeningitis virus (LCMV). In these mice, LCMV spread from the spleen to peripheral organs at an early phase of infection. The virus‐specific cytotoxic T lymphocyte (CTL) response was induced initially, yet was exhausted in parallel with the overwhelming virus replication. These findings suggest that MZM and MM play a crucial role in the early control of a LCMV infection by preventing immediate virus spread to peripheral organs, but are not essential for the induction of the LCMV‐specific CTL response.
Comparison of the effects of interleukin‐1α, interleukin‐lβ and interferon‐γ‐inducing factor on the production of interferon‐γ by natural killer
Authors: Hunter Christopher A. , Timans Jackie , Pisacane Paul , Menon Satish , Cai Guifang , Walker William , Aste‐Amezaga Miguel , Chizzonite Richard , Bazan J. Fernando , Kastelein Robert A. 
Published: March 2007

AbstractInterferon‐γ inducing factor (IGIF) is a recently identified cytokine which stimulates the production of interferon‐γ (IFN‐γ) by T cells and enhances natural killer (NK) cell cytolytic activity. Protein fold recognition, structure prediction and comparative modeling have revealed that IGIF is a member of the interleukin (IL)‐1 cytokine family and has prompted the designation IL‐1γ. Here we report functional similarities between members of the IL‐1 family by comparing the effects of IL‐1α, IL‐1β and IGIF on NK cell production of IFN‐γ. All three IL‐1 types enhanced NK cell production of IFN‐γ when induced by IL‐2 or IL‐12, although at high concentrations (>10 ng/ml), IGIF was five‐ to tenfold more potent than IL‐1α or IL‐1β. This effect correlated with enhanced levels of mRNA for IFN‐γ when NK cells were stimulated with IGIF plus IL‐12. In contrast to IL‐12 and IL‐2, the ability of IGIF to stimulate NK cell production of IFN‐γ was not increased by IL‐1α or IL‐1β. The ability of IGIF to enhance IFN‐γ production was independent of the type I and type II IL‐1 receptors or the IL‐1R accessory protein. Together, these results identify IGIF as a potent stimulator of NK cell production of IFN‐γ and demonstrate that the effect of IGIF on NK cell production of IFN‐γ is similar to that of IL‐1α and IL‐1β but distinct from that of IL‐12.
CD4+ T cells of both the naive and the memory phenotype enter rat lymph nodes and Peyer's patches via high endothelial venules: Within the tissue their migratory behavior differs
Authors: Westermann Jürgen , Geismar Ulrike , Sponholz Angélique , Bode Ulrike , Sparshott Sheila M. , Bell Eric B. 
Published: March 2007

AbstractIt is thought that naive T cells predominantly enter lymphoid organs such as lymph nodes (LN) and Peyer's patches (PP) via high endothelial venules (HEV), whereas memory T cells migrate mainly into non‐lymphoid organs. However, direct evidence for the existence of these distinct migration pathways in vivo is incomplete, and nothing is known about their migration through the different compartments of lymphoid organs. Such knowledge would be of considerable interest for understanding T cell memory in vivo. In the present study we separated naive and memory CD4+ T cells from the rat thoracic duct according to the expression of the high and low molecular weight isoforms of CD45R, respectively. At various time points after injection into congenic animals, these cells were identified by quantitative immunohistology in HEV, and T and B cell areas of different LN and PP. Three major findings emerged. First, both naive and memory CD4+ T cells enter lymphoid organs via the HEV in comparable numbers. Second, naive and memory CD4+ T cells migrate into the B cell area, although in small numbers and continuously enter established germinal centers (GC) with a bias for memory CD4+ T cells. Third, memory CD4+ T cells migrate faster through the T cell area of lymphoid organs than naive CD4+ T cells. Thus, our study shows that memory CD4+ T cells are not excluded from the HEV route. In addition, “memory” might depend in part on the ability of T cells to specifically enter the B cell area and GC and to screen large quantities of lymphoid tissues in a short time.
Cross talk between αvβ3 and α4β1 integrins regulates lymphocyte migration on vascular cell adhesion molecule 1
Authors: Imhof Beat A. , Weerasinghe Dheepika , Brown Eric J. , Lindberg Frederic P. , Hammel Philippe , Piali Luca , Dessing Mark , Gisler Roland 
Published: March 2007

AbstractLocal inflammation leads to increased expression of the vascular cell adhesion molecule (VCAM)‐1 on vascular endothelium which contributes to the encapture of leukocytes from the circulating blood through the leukocyte ligand α4β1 integrin. Inflammatory vascular endothelium expresses VCAM‐1 at high density. We found that the speed of locomotion of activated lymphocytes migrating along surfaces coated with recombinant VCAM‐1 at a comparable density to that found on inflammatory endothelium was slow. However, lymphocytes do migrate and extravasate rapidly under inflammatory conditions, indicating that there must be mechanisms that regulate the interaction between α4β1 and VCAM‐1 in vivo. Here we show that the lymphocyte αβ3 integrin and integrin‐associated protein (IAP) is able to regulate this interaction. The occupancy of lymphocyte αvβ3 integrin by platelet cell adhesion molecule‐1 or vitronectin regulated the speed of α4β3 integrin‐dependent locomotion of lymphocytes on recombinant VCAM‐1. This allowed rapid lymphocyte migration at VCAM‐1 densities which are typical of inflammatory vessels. This αvβ3‐mediated enhanced migration of lymphocytes via α4β1 is likely to depend on the interaction of αvβ3 integrin with the IAP. Furthermore, this motile process correlates with polarization of the actin cytoskeleton in lymphocytes. Our results suggest that cross talk between αvβ3 integrin and α4β1 integrin is a mechanism in the regulation of lymphocyte locomotion along inflammatory endothelium and subsequent transendothelial migration. This can explain how lymphocytes overcome tight adhesion to the vascular endothelium and start rapid migration along and through the endothelial lining of blood vessels into inflammatory tissue.
Single‐cell analysis of intrathyroidal lymphocytes shows differential cytokine expression in Hashimoto's and Graves' disease
Authors: Roura‐Mir Carme , Catálfamo Marta , Sospedra Mireia , Alcalde Laura , Pujol‐Borrell Ricardo , Jaraquemada Dolores 
Published: March 2007

AbstractMost human organ‐specific autoimmune diseases such as Hashimoto's thyroiditis (HT) are considered to be Th1 mediated, and a quantitative dominance of Th1 cells in thyroid infiltrates from both Graves' disease (GD) and HT affected glands has been reported. However, Th2 dominance would be expected in GD, where thyroid hyperfunction induced by stimulating antibodies predominates over tissue destruction. We have analyzed the interleukin‐4 (IL‐4), interferon‐γ (IFN‐γ) production by T cells at the single‐cell level, both in infiltrating lymphocytes isolated from digested GD and HT thyroid glands and in derived T cell lines, by direct intracellular cytokine detection. Results showed a heterogeneous pattern of cytokine production in bulk GD infiltrates and derived T cell lines, and a similar pattern was observed in the much larger HT infiltrates. Both type 1 and type 2 cytokines were simultaneously produced by the infiltrating populations, and T cells with both patterns as well as intermediate patterns similar to ThO cells could be detected ex vivo. However, the larger T lymphocytes, presumably activated and responsible for the autoimmune damage, predominantly produced IL‐4 in GD and IFN‐γ in HT. The specificity of the Th2 responses in GD was suggested by the enrichment in IL‐4 production after antigen‐specific expansion of two oligoclonal T cell lines. These data show that both type 1 and type 2 cytokines are produced in the thyroid glands affected by autoimmunity and that the difference between diseases may be the effect of a functionally dominant population at a given time. This in vivo chronically activated antigen‐specific population, producing type 1 or type 2 cytokines locally, may be responsible for the effect finally leading to one of the disease states.
Voltammetric Study of Reduction Processes in Rhodium(+3)–Selenium(+4) Acidic Mixtures
Authors: Zelić Marina , Strmečki Slađana 
Published: March 2007

AbstractUsing square‐wave voltammetry and linear scan voltammetry, some reduction processes, that take place on the hanging mercury drop electrode (HMDE) in rhodium(+3)–selenium(+4) mixtures, were studied in highly acidic sulfate, chloride and perchlorate solutions. The special attention was paid to the peak located at −1.1 V, that reflects catalytic hydrogen evolution on the rhodium islets, and its changes under the influence of added selenium(+4), or selenium(−2) produced at the electrode. It can be concluded that addition of selenite to a dilute rhodium solution has the similar effect as the increase of rhodium(+3) concentration, making the catalytic hydrogen evolution more pronounced, probably by changing the properties of metal clusters on the mercury drop. If so, the effect could be of some practical importance in production of rhodium deposits on other surfaces, too.
Electroanalytical Study of the Composition of the Raw Pigment Mixtures that Yield the Metallic Lustre on Ceramics. A Link Between Composition and Final Result
Authors: Cepriá G. , Roque J. , Molera J. , Pérez‐Arantegui J. , Vendrell M. 
Published: March 2007

AbstractVoltammetry of immobilized microparticles was used to study the electrochemistry of the raw pigments that produce the metallic lustre on ceramics after a successful firing. To study this influence of the mixture components on the reduction properties to achieve the metallic lustre, 14 mixtures of illitic clay, Fe2O3, HgS, CuO and AgNO3 were prepared and studied in different media. Iron oxide improves the yield of the reduction of the metals and cinnabar helps a closer reduction of silver to copper reduction and prevents the AgCu alloying because of the formation of silver–mercury adducts. The presence of one of the metals influences the peak position of the other metal. The use of vinegar as diluting agent is not casual, because in this media the reduction of silver takes place at a potential closer to the copper. This electroanalytical technique allowed to distinguish between powders of different composition and offered some information about the role of the components in the reduction of copper and silver and the selection of vinegar to prepare the raw pigment suspensions.