bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses
Authors: Oliver Alyce M. , Martin Flavius , Gartland G. Larry , Carter Robert H. , Kearney John F. 
Published: March 2007

AbstractMouse splenic B cells can be separated based on their distinctive expression of cell surface antigens. Marginal zone (MZ) B cells are CD38high CD21high CD23low/−, while follicular (FO) B cells are CD21int CD23int and newly formed (NF) B cells are CD21dim/− CD23−. Exploiting these phenotypic distinctions, we isolated the three B cell subsets and assessed their other phenotypic differences and functional capabilities in vitro. FO B cells proliferate more than the other B cell subsets in response to either IgM or CD38 cross‐linking. MZ B cells proliferate better than FO B cells when stimulated with lipopolysaccharide (LPS), sub‐optimal levels of LPS and CD38 cross‐linking or CD40 ligation. When NF, FO and MZ B cells were stimulated with either LPS or LPS and interleukin‐4, MZ B cells secreted more IgM and IgG3 than the other two subsets. Similarly, calcium fluxes measured within MZ B cells are larger in amplitude and more sustained after B cell receptor cross‐linking than those found in the other two subsets. Collectively, these results indicate that CD38high CD21high CD23low/− MZ B cells are specially suited to play a unique role in response to antigens delivered to the MZ area.
Genetic modification of a carcinoma with the IL‐4 gene increases the influx of dendritic cells relative to other cytokines
Authors: Stoppacciaro Antonella , Paglia Paola , Lombardi Luciano , Parmiani Giorgio , Baroni Carlo , Colombo Mario P. 
Published: March 2007

AbstractTumor cells genetically modified with certain cytokine genes gain immunogenic properties that allow the development of systemic anti‐tumor immunity. Whether different cytokines may influence infiltration of transduced tumors by dendritic cells (DC) has not been investigated. Therefore, we analyzed the C26 murine colon carcinoma genetically modified to release interleukin (IL)‐2, IL‐4, IL‐12, granulocyte colony‐stimulating‐factor (CSF) or granulocyte‐macrophage (GM)‐CSF for immunostaining with the monoclonal antibody NDLC145 recognizing the DEC205 determinant which, on tumor sections, is virtually restricted to DC. Infiltrating leukocytes were also characterized for expression of co‐stimulatory molecules like CD54, CD86 and major histocompatibility complex class II. The intratumoral DC content was dependent on the type of transduced cytokines with C26/IL‐4 being the most abundant in DEC205+ cells. The effect of IL‐4 in recruiting DC did not depend on the type of tumor since it was confirmed in the TSA mammary carcinoma. In comparison with C26/GM‐CSF, C26/IL‐4 had more B7.2+ cells but less Ia+ cells. Furthermore, the hypertrophic skin overlaying tumors producing GM‐CSF showed numerous Langerhans cells stained by NDLC145 and the draining lymph nodes showed abundance and paucity of DC in C26/GM‐CSF and C26/IL‐4, respectively. When injected into the ear pinna, C26/GM‐CSF stimulated, whereas C26/IL‐4 inhibited DC‐mediated priming of delayed‐type hypersensitivity reaction by 2,4‐dinitro‐1‐fluorobenzene. These findings prove that transduced cytokines differently influence DC recruitment at the tumor site and DC function in nearby tissues. Along with the other leukocytes and their secondary produced cytokines, DC create an environment in which T cells can be differently modulated. Such a phenomenon may have implications on genetic modification of tumor cells to be used as cancer vaccine.
Priming of cytotoxic T lymphocytes by five heat‐aggregated antigens in vivo: Conditions, efficiency, and relation to antibody responses
Authors: Speidel Katharina , Osen Wolfram , Faath Stefan , Hilgert Ivan , Obst Reinhard , Braspenning Joris , Momburg Frank , Hämmerling Günter J. , Rammensee Hans‐Georg 
Published: March 2007

AbstractMice were immunized i.p. with soluble or heat‐denatured protein antigens [ovalbumin, β‐galactosidase, or recombinant E7 protein of human papilloma virus type 16 (HBV)]. Heat‐denatured (100°C) preparations of these proteins were able to induce cytotoxic T lymphocytes (CTL) that recognize cells expressing the respective genes, whereas native protein was either inefficient or required up to 30‐fold higher doses. If the heat‐treated proteins were separated into aggregated and soluble fractions by ultracentrifugation, only the aggregated fractions were able to induce specific CTL; this is probably because of the easier access to one of the major histocompatibility complex class I loading pathways for exogenous antigen. Addition of the adjuvant aluminium hydroxide (alum) to aggregated proteins abolished their ability to induce CTL; thus, a condition leading to a strong antibody response appeared to inhibit CTL induction. Interestingly, immunization with heat‐denatured ovalbumin plus alum increased the IgM/IgG1 ratio compared to immunization with native ovalbumin and alum. Immunization of B6 mice transgenic for an HLA‐A2/H‐2Kb hybrid gene with heat‐denatured, recombinant HPV 16‐E7 protein induced Db‐restricted CTL specific for the peptide 49–57 of E7, indicating that this epitope is immunodominant over any A2‐restricted E7 epitope in these mice. A whole influenza virus preparation heated to 100°C or even autoclaved was still able to induce virus‐specific CTL and BALB/c spleen cells heated to 100°C could still cross‐prime minor H‐specific CTL in B6 mice, although with lower efficiency than fresh spleen cells. Thus, aggregated proteins can be considered as components for future vaccines.
Priming of helper T cell‐dependent antibody responses by hemagglutinin‐transgenic B cells
Authors: Kalberer Christian P. , Reininger Luc , Melchers Fritz , Rolink Antonius G. 
Published: March 2007

AbstractMice expressing the hemagglutinin (HA) gene of influenza virus PR8 (H1 subtype) under the control of x light chain promoter and enhancer have been generated. They express HA in and on B cells, and are tolerant to HA. In vitro, only lipopolysaccharide (LPS) blasts but not resting B cells of transgenic mice can stimulate HA‐specific helper T cells of HA‐specific α/β T cell receptor (TCR)‐transgenic mice. Transfer of HA‐transgenic LPS blasts into syngeneic, non‐transgenic recipients primes HA‐specific antibody responses. Resting, small HA‐transgenic B cells, which were purified by fluorescence‐activated cell sorting, prime lower antibody responses. Host B cells produce the HA‐specific antibody response. The donor HA‐transgenic B cells need to express major histocompatibility complex (MHC) class II molecules and need to be alive to induce the antibody response in the host. Most notably, the host antibody response never produces detectable levels of IgM, but only of switched IgG isotypes. Neither resting nor activated HA‐transgenic B cells induce tolerance in antibody responses. These results suggest that HA‐transgenic B cells, presenting both the intact antigen on the cell surface and peptides of the antigen on MHC class II, are effective inducers of helper T cell responses, and as judged by the Ig‐isotype response pattern, which is mainly IgG1, of Th2 type.
Mannose receptor‐mediated uptake of antigens strongly enhances HLA class II‐restricted antigen presentation by cultured dendritic cells
Authors: Tan M. C. Agnes A. , Mommaas A. Mieke , Drijfhout Jan Wouter , Jordens Reina , Onderwater Jos J. M. , Verwoerd Desiree , Mulder Aat A. , van der Heiden Annette N. , Scheidegger Doris , Oomen Lauran C. J. M. , Ottenhoff Tom H. M. , Tulp Abraham , Neefjes Jacques J. , Koning Frits 
Published: March 2007

AbstractDendritic cells (DC) efficiently take up antigens by macropinocytosis and mannose receptor‐mediated endocytosis. Here we show that endocytosis of mannose receptor‐antigen complexes takes place via small coated vesicles, while non‐mannosylated antigens were mainly present in larger vesicles. Shortly after internalization the mannose receptor and its ligand appeared in the larger vesicles. Within 10 min, the mannosylated and non‐mannosylated antigens co‐localized with typical markers for major histocompatibility complex class II‐enriched compartments and lysosomes. In contrast, the mannose receptor appeared not to reach these compartments, suggesting that it releases its ligand in an earlier endosomal structure. Moreover, we demonstrate that mannosylation of protein antigen and peptides resulted in a 200–10 000‐fold enhanced potency to stimulate HLA class II‐restricted peptide‐specific T cell clones compared to non‐mannosylated peptides. Our results indicate that mannosylation of antigen leads to selective targeting and subsequent superior presentation by DC which may be applicable in vaccine design.
Monoclonal gammopathies in aging μ, x‐transgenic mice: Involvement of the B‐1 cell lineage
Authors: van Arkel Cornelis , Hopstaken Cornelis M. , Zurcher Chris , Bos Nicolaas A. , Kroese Frans G. M. , Savelkoul Huub F. J. , Benner Robbert , Radl Jiri 
Published: March 2007

AbstractMonoclonal gammopathies (MG) are monoclonal proliferative disorders of B cells at the differentiation stage of Ig production. They can be detected in the serum, either as transient or as persistent homogenous immunoglobulin (H‐Ig) components. The exact phenotype, localization, and cell lineage origin of the precursor cells of MG are unknown, but may be crucial for both the correct diagnosis and for timely efficient treatment of the malignant forms. We used for the first time transgenic (Tg) mice (Sp6; μ/x) to study the origin of MG. In the μ, x Tg mice a small proportion of B cells can still produce endogenous IgM. These cells are of B‐1 cell origin. The MG in Tg mice showed a later onset and a lower frequency than those in littermate control mice, mainly due to a four times lower frequency of benign monoclonal gammopathy. The 10% of B‐1 cells that were able to produce endogenous Ig led to the development of MG in a frequency that was half the number of MG found in normal littermates. None of the MG in Tg mice produced an Ig of the Tg origin and therefore it can be concluded that they originated from B‐1 cells.
Down‐regulation of LFA‐1‐mediated T cell adhesion induced by the HIV envelope glycoprotein gp160 requires phosphatidylinositol‐3‐kinase activity
Authors: Mazerolles Fabienne , Barbat Christiane , Fischer Alain 
Published: March 2007

AbstractHuman immunodeficiency virus binds to CD4+ T lymphocyte by the interaction, in part, between its gp120 envelope glycoprotein and the CD4 molecule. We and others have reported that the lipid kinase phosphatidylinositol‐3‐kinase (PI3‐kinase) is associated with the CD4‐p56lck complex and can be activated by various CD4 ligands. In a previous report we showed that the gp160 envelope down‐regulates lymphocyte function‐associated antigen‐1 (LFA‐1)‐dependent adhesion between CD4+ T cells and B cells. This down‐regulation was shown to be p56lck‐dependent. Here we investigate the role of PI3‐kinase in the inhibition of adhesion induced by gp160 binding to CD4. We found that gp160 activates the PI3‐kinase of HUT78 CD4+ T cell lines in a way dependent on CD4‐p56lck association, since no activation was detected when the interaction between CD4 and p56lck was disrupted. It was also shown, using different inhibitors of the PI3‐kinase (wortmannin, Ly294002 and antisense oligonucleotides), that this lipid kinase was necessary for the down‐regulation of LFA‐1‐mediated adhesion induced by gp160. These results strongly suggest that PI3‐kinase activation induced by gp160 leads to down‐regulation of LFA‐1‐mediated T cell adhesion to B cells. Inhibition by gp160 of cytoskeleton rearrangement‐dependent, anti‐CD3‐mediated T cell adhesion to B cells was blocked by neutralization of PI3‐kinase activity, while inhibition of cytoskeleton rearrangement‐independent, Mg2+‐induced T cell adhesion was not. These results emphasize the role of PI3‐kinase in the regulation of cytoskeleton structure. It is proposed that gp160 activates both p56lck and PI3‐kinase which lead to a cytoskeleton organization unfavorable for LFA‐1 function.
Interleukin‐9 is involved in host protective immunity to intestinal nematode infection
Authors: Faulkner Helen , Humphreys Neil , Renauld Jean‐Christophe , van Snick Jacques , Grencis Richard 
Published: March 2007

AbstractMurine studies have demonstrated that, as with other nematodes, infection with the intestinal nematode Trichinella spiralis is associated with a pronounced intestinal mastocytosis, eosinophilia and an elevation in serum levels of total IgE. Both interleukin (IL)‐4 and IL‐5 are clearly important in the generation of IgE responses and eosinophilia, respectively, but the control of mucosal mastocytosis in vivo is not as well defined. Mucosal mast cells appear to be particularly important with regard to T. spiralis infections as there is good evidence to suggest their involvement in expulsion of the parasite from the host. In this study we examined the effect of the overproduction of the Th2 cytokine IL‐9 on infection with this nematode. We demonstrate that naive IL‐9‐transgenic mice have an intense intestinal mastocytosis and high serum levels of mouse mast cell protease‐1. Moreover, upon infection high titers of parasite‐specific IgG1 were observed with a heightened mast cell response, which was associated with the rapid expulsion of T. spiralis from the gut. Furthermore, as depression of this mast cell response, using anti‐c‐kit antibodies, resulted in the inability of these mice to expel the parasite, this study clearly demonstrates an activity of IL‐9 on mucosal mastocytosis and the host protective immune response in vivo.
Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix‐bound interleukin‐7
Authors: Ariel Amiram , Hershkoviz Rami , Cahalon Liora , Williams Douglas E. , Akiyama Steven K. , Yamada Kenneth M. , Chen Chun , Alon Ronen , Lapidot Tsvee , Lider Ofer 
Published: March 2007

AbstractThe putative effects of interleukin (IL)‐7, operating in the context of extracellular matrix (ECM), on the adhesion of human T cells were examined. Recombinant human IL‐7 was found to bind ECM or fibronectin (FN) with IC50 values of 10–100 nM. Nanogram amounts of both soluble and, especially, FN‐ or ECM‐bound IL‐7, which differentially affected the morphologies of FN‐adherent T cells, induced the adhesion of resting CD4+ and CD8+ T cells in dose‐dependent and β1 integrin‐dependent manners. Under static and flow conditions, soluble IL‐7 also induced the binding of unstimulated T cells to vascular cell adhesion molecule‐1, suggesting that this cytokine can also modulate integrin binding to endothelial cell ligands. The effects of affinity modulation by IL‐7 of FN‐specific β1 integrins depend on the presence of soluble FN, which inhibited T cell adhesion to FN induced by FN‐bound IL‐7 or by an integrin‐specific affinity‐modulating monoclonal antibody, but not by soluble IL‐7 or phorbol 12‐myristate 13‐acetate. These findings provide an example of a major ECM integrin ligand, FN, which is capable of modulating its adhesive interactions with specific immune cells by associating with and presenting a cytokine in a bio‐active state.
Chemoattractant receptor cross talk as a regulatory mechanism in leukocyte adhesion and migration
Authors: Campbell James J. , Foxman Ellen F. , Butcher Eugene C. 
Published: March 2007

AbstractLeukocytes express multiple chemoattractant receptors that can trigger adhesion and direct their migration. Regulation of such proadhesive and migratory responses must often occur in a complex cytokine milieu in vivo, in which multiple receptors may be engaged simultaneously or sequentially, Here we have examined the interplay between interleukin‐8 (IL‐8) receptor and formyl peptide receptor (fPR) stimulation and its consequences for leukocyte adhesion and chemotactic responses. IL‐8 has no significant effect on fMLP‐stimulated adhesion and migration of human neutrophils, indicating that leukocytes have the potential to respond to sequential proadhesive and chemoattractant stimuli during homing and targeted migration. In contrast, fMLP at ⩾ 10 nM totally abrogated proadhesive and chemoattractant responses to IL‐8, a trans effect to which the fPR itself is relatively resistant. N‐formyl peptides are released by invasive bacteria and lysed cells, and the dominance of the fPR may ensure that signals from these terminal phagocyte targets can override host‐derived recruitment signaling through IL‐8 and other chemokine receptors. Asymmetric inhibition of adhesion‐triggering responses is also observed in lymphoid cells transfected with IL‐8 receptor A and fPR, but in this cellular context chemotactic responses are bidirectionally abrogated, suggesting the potential for downstream desensitization of motility programs as well. Cross talk between chemoattractant receptors and their signaling pathways may help target leukocyte migration in the context of complex chemoattractant arrays in vivo.
Distinct roles for lymphotoxin‐α and tumor necrosis factor in organogenesis and spatial organization of lymphoid tissue
Authors: Körner Heinrich , Cook Matthew , Riminton D. Sean , Lemckert Frances A. , Hoek Robert M. , Ledermann Birgit , Köntgen Frank , de St Groth Barbara Fazekas , Sedgwick Jonathon D. 
Published: March 2007

AbstractSpecialized roles for the pro‐inflammatory cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) were characterized in TNF/LTα−/− and TNF−/− mice established by direct gene targeting of C57BL/6 ES cells. The requirement for LT early in lymphoid tissue organogenesis is shown to be distinct from the more subtle and varied role of TNF in promoting correct microarchitectural organization of leukocytes in LN and spleen. Development of normal Peyer's patch (PP) structure, in contrast, is substantially dependent on TNF. Only mice lacking LT exhibit retarded B cell maturation in vivo and serum immunoglobulin deficiencies. A temporal hierarchy in lymphoid tissue development can now be defined, with LT being an essential participant in general lymphoid tissue organogenesis, developmentally preceeding TNF that has a more varied and subtle role in promotion of correct spatial organization of leukocytes in LN and spleen. PP development in TNF−/− mice is unusual, indicating that TNF is a more critical participant for this structure than it is for other lymphoid tissues.
Co‐localization of Fyn with CD3 complex, CD45 or CD28 depends on different mechanisms
Authors: zur Hausen Jan Dirk , Burn Paul , Amrein Kurt E. 
Published: March 2007

AbstractThe Src family protein tyrosine kinase Fyn (p59fyn) plays an important role in thymocyte development and T cell receptor (TCR) signal transduction. Fyn has been shown to associate with the TCR‐CD3 complex, the protein tyrosine phosphatase CD45 and several co‐receptors such as CD28 which are crucial for initiating T cell activation and proliferation. The molecular basis of how Fyn is associated with these transmembrane proteins is largely unknown. To investigate the Fyn association with the TCR‐CD3 complex, CD45 and CD28 at the molecular level, various Fyn/β‐galactosidase fusion proteins were constructed and expressed in Jurkat cells. Co‐localization experiments applying antibody‐induced co‐capping and double immunofluorescence staining techniques were used to study the association of these fusion proteins with the TCR‐CD3 complex, CD45 and CD28. Our results revealed that co‐localization of Fyn with the TCR‐CD3 complex requires the unique N terminus whereas co‐localization with CD45 depends on the unique N terminus, the Src homology (SH)3‐ and a functional SH2 domain. CD28 co‐localizes with Fyn molecules that contain the N terminus and a functional SH2 domain. These results suggest that Fyn association with the TCR‐CD3 complex, CD45 and CD28 is mediated by different molecular mechanisms.
Ultrastructural analysis of mouse thymocyte subpopulations
Authors: Yagi Hideki , Nakamura Masanori , Ishii Tadashi , Kasahara Shigeru , Itoh Tsunetoshi 
Published: March 2007

AbstractTo understand the lineage relationship and to define morphological characteristics of each thymocyte subset, we have performed ultrastructural analysis of highly purified thymocyte subpopulations. By flow cytometry, five subpopulations were sorted based on the expression of CD4 and CD8 and on cell size (forward scatter): large and small CD4+8+, CD4−8−, CD4+8−, and CD4−8+ thymocytes. Small CD4+8+ thymocytes were the smallest among lymphoid cells, and had a round and smooth cell outline with condensed nuclei, the cytoplasm was scanty and the cell organelles were not developed, suggesting the majority of this subset might be inactive by morphological criteria. CD4+8− thymocytes appeared to be similar to peripheral CD4+ T cells. The CD4−8− thymocyte subset contained morphologically immature cells in terms of cell size, presence of cell surface villi, and euchromatic appearance of the nucleus. CD4−8+ thymocytes, heterogeneous in cell size, nuclear chromatin contents and amount of cytoplasm, could be divided into two distinct types. Type 1 CD4−8+ thymocytes were intermediate in size, and therefore similar to peripheral mature CD8+ T cells. Type 2 CD4−8+ thymocytes were large and irregular in shape (large CD4−8+) with irregular‐shaped and euchromatic nuclei. Large CD4−8+ cells were, thus, considered to be at the transitional stage from CD4−8− to CD4+8+. At least two groups of large CD4+8+ cells were ultrastructurally classified by the nuclear chromatin content. Large CD4+8+ cells with heterochromatic nuclei were round with a smooth cell membrane, whereas large CD4+8+ cells with euchromatic nuclei were spherical with projections. Cytological features of heterochromatic large CD4+8+ cells are similar to those of small CD4+8+ thymocytes except for cell size. Euchromatic large CD4+8+ cells could be regarded as active blasts potentially leading to mature cells. Taken together, this is the first report that describes the ultrastructural characteristics of each thymocyte subset highly purified by flow cytometry.
Host cell factor CD59 restricts complement lysis of Plasmodium falciparum‐infected erythrocytes
Authors: Wiesner Jochen , Jomaa Hassan , Wilhelm Martin , Tony Hans‐Peter , Kremsner Peter G. , Horrocks Paul , Lanzer Michael 
Published: March 2007

AbstractHere we demonstrate that components of the entire complement cascade are fixed on the surface of erythrocytes infected with the human malarial parasite Plasmodium falciparum. Despite the activation of lytic complement factors, no complement‐mediated lysis of parasitized erythrocytes was observed. Complement‐mediated lysis of P. falciparum‐infected erythrocytes occurred only in the absence of functional intrinsic CD59. These data suggest that the restriction of the complement attack of P. falciparum‐infected erythrocytes is principally mediated by intrinsic host cell factors, in particular CD59.
Rho prevents apoptosis through Bcl‐2 expression: Implications for interleukin‐2 receptor signal transduction
Authors: Gómez Javier , Martínez‐A. Carlos , Giry Murielle , García Alphonse , Rebollo Angelita 
Published: March 2007

AbstractHere we describe a Rho‐mediated apoptosis suppression pathway driven by Bcl‐2 expression in the interleukin (IL)‐4‐ or IL‐2‐dependent murine T cell line TS1αβ. IL‐2, but not IL‐4, induces Bcl‐2 expression through RhoA activation which is inhibited by the specific Rho family inhibitor, Clostridium difficile Toxin B, as well as by a dominant negative RhoA mutant. Using transient transfections of RhoA mutants tagged with the vesicular stomatitis virus glycoprotein, we show that a constitutively active RhoA mutant induces Bcl‐2 expression and prevents apoptosis upon IL‐4 withdrawal. Finally, we have identified the signaling pathway involved together with RhoA in Bcl‐2 induction and show compelling evidence for the implication of phosphatidylinositol 3 kinase and protein kinase C.