bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a new subpopulation of mouse CD8α+ B220+ dendritic cells endowed with type 1 interferon production capacity and tolerogenic potential
Authors: Martı́n Pilar , del Hoyo Gloria Martı́nez , Anjuère Fabienne , Arias Cristina Fernández , Vargas Héctor Hernández , Fernández-L Africa , Parrillas Verónica , Ardavı́n Carlos 
Published: October 2002

AbstractWe describe a new B220+ subpopulation of immaturelike dendritic cells (B220+ DCs) with low levels of expression of major histocompatibility complex (MHC) and costimulatory molecules and markedly reduced T-cell stimulatory potential, located in the thymus, bone marrow, spleen, and lymph nodes. B220+ DCs display ultrastructural characteristics resembling those of human plasmacytoid cells and accordingly produce interferon-α after virus stimulation. B220+ DCs acquired a strong antigen-presenting cell capacity on incubation with CpG oligodeoxynucleotides, concomitant with a remarkable up-regulation of MHC and costimulatory molecules and the production of interleukin-12 (IL-12) and IL-10. Importantly, our data suggest that nonstimulated B220+ DCs represent a subset of physiological tolerogenic DCs endowed with the capacity to induce a nonanergic state of T-cell unresponsiveness, involving the differentiation of T regulatory cells capable of suppressing antigen-specific T-cell proliferation. In conclusion, our data support the hypothesis that B220+ DCs represent a lymphoid organ subset of immature DCs with a dual role in the immune system—exerting a tolerogenic function in steady state but differentiating on microbial stimulation into potent antigen-presenting cells with type 1 interferon production capacity.
The N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated endothelium via P-selectin in vivo
Authors: Burch Erin E. , Patil Vivek R. Shinde , Camphausen Raymond T. , Kiani Mohammad F. , Goetz Douglas J. 
Published: October 2002

AbstractP-selectin glycoprotein ligand-1 (PSGL-1) is present on leukocytes and is the major ligand for endothelial expressed P-selectin. A variety of studies strongly suggests that the N-terminal region of PSGL-1 contains the binding site for P-selectin. We hypothesized that this relatively small N-terminal peptide of PSGL-1 is sufficient to support adhesion to P-selectin in vivo. To test this hypothesis, we coated 2 μm–diameter microspheres with a recombinant PSGL-1 construct, termed 19.ek.Fc. The 19.ek.Fc construct consists of the first 19 N-terminal amino acids of mature PSGL-1 linked to an enterokinase cleavage site that, in turn, is linked to human immunoglobulin G Fc. The 19.ek.Fc-coated microspheres were injected into the jugular vein of mice. Intravital microscopy of postcapillary venules within the cremaster muscle of mice revealed that a significantly greater number of 19.ek.Fc microspheres rolled compared with control microspheres. The number of rolling 19.ek.Fc microspheres was significantly diminished by pretreatment of the mice with a monoclonal antibody to P-selectin or by pretreatment of the 19.ek.Fc microspheres with a monoclonal antibody to PSGL-1. Combined, the results indicate that the N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated microvascular endothelium via P-selectin in vivo.
Induced disruption of the transforming growth factor beta type II receptor gene in mice causes a lethal inflammatory disorder that is transplantable
Authors: Levéen Per , Larsson Jonas , Ehinger Mats , Cilio Corrado M. , Sundler Martin , Sjöstrand Lottie Jansson , Holmdahl Rikard , Karlsson Stefan 
Published: October 2002

AbstractRecent studies in mouse models deficient in transforming growth factor beta (TGF-β) signaling have documented TGF-β as one of the major regulators of immune function. TGF-β1–null animals demonstrated massive autoimmune inflammation affecting multiple organs, but attempts to transfer the phenotype to normal animals by bone marrow transplantation only resulted in minor inflammatory lesions. We wanted to ask whether a lethal inflammatory phenotype would develop following transplantation of bone marrow deficient for the TGF-β type II receptor (TβRII) gene to normal recipient animals. The TβRII-null mutation would generate a cell autonomous phenotype that cannot be reverted by the influence of endocrine or paracrine TGF-β derived from the recipient animal. We have generated conditional knockout mice in which the TβRII gene is disrupted upon induction with interferon-αβ or polyI:polyC. We show that induction of TβRII gene disruption in these mice by polyI:polyC results in a lethal inflammatory disease. Importantly, bone marrow from conditional knockout mice transferred to normal recipent mice caused a similar lethal inflammation, regardless of whether induction of TGF-β receptor deficiency occurred in donor animals before, or in recipient animals after transplantation. These results show that TGF-β signaling deficiency within cells of hematopoietic origin is sufficient to cause a lethal inflammatory disorder in mice. This animal model provides an important tool to further clarify the pathogenic mechanisms in animals deficient for TGF-β signaling and the importance of TGF-β to regulate immune functions.
MUTZ-3, a human cell line model for the cytokine-induced differentiation of dendritic cells from CD34+precursors
Authors: Masterson Allan J. , Sombroek Claudia C. , de Gruijl Tanja D. , Graus Yvo M. F. , van der Vliet Hans J. J. , Lougheed Sinéad M. , van den Eertwegh Alfons J. M. , Pinedo Herbert M. , Scheper Rik J. 
Published: October 2002

AbstractMany human myeloid leukemia–derived cell lines possess the ability to acquire a dendritic cell (DC) phenotype. However, cytokine responsiveness is generally poor, requiring direct manipulation of intracellular signaling mechanisms for differentiation. In contrast, the CD34+ human acute myeloid leukemia cell line MUTZ-3 responds to granulocyte macrophage– colony-stimulating factor (GM-CSF), interleukin 4 (IL-4), and tumor necrosis factor alpha (TNFα), cytokines known to be pivotal both in vivo and in vitro for DC generation from monocytes and CD34+ stem cells. In all respects, MUTZ-3 cells behave as the immortalized equivalent of CD34+ DC precursors. Upon stimulation with specific cytokine cocktails, they acquire a phenotype consistent with either interstitial- or Langerhans-like DCs and upon maturation (mDC), express CD83. MUTZ-3 DC display the full range of functional antigen processing and presentation pathways. These findings demonstrate the unique suitability of MUTZ-3 cells as an unlimited source of CD34+DC progenitors for the study of cytokine-induced DC differentiation.
Analysis of the hematopoietic potential of muscle-derived cells in mice
Authors: Geiger Hartmut , True Jarrod M. , Grimes Barry , Carroll Elizabeth J. , Fleischman Roger A. , Van Zant Gary 
Published: October 2002

Abstract
Cells in murine muscle have been reported to differentiate into hematopoietic stem and progenitor cells and thus repopulate the hematopoietic system of an irradiated animal. This activity was attributed to muscle stem cells. We used an in vitro and in vivo approach to identify the hematopoietic repopulating activity found in muscle tissue of mice by antibody staining and cell sorting. We confirmed existence of a hematopoietic repopulating cell in muscle tissue, but the data strongly suggest that repopulation is due not to muscle stem cells but to hematopoietic cells present in muscle tissue. Unexpectedly, the blood-forming cells were enriched in muscle relative to their frequency in peripheral blood.
Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia
Authors: Pedersen-Bjergaard Jens , Andersen Mette K. , Christiansen Debes H. , Nerlov Claus 
Published: October 2002

Abstract
Therapy-related acute myeloid leukemia (t-AML) in most cases develops after chemotherapy of other malignancies and shows characteristic chromosome aberrations. Two general types of t-AML have previously been identified. One type is observed after therapy with alkylating agents and characteristically presents as therapy-related myelodysplasia with deletions or loss of the long arms of chromosomes 5 and 7 or loss of the whole chromosomes. The other type is observed after therapy with topoisomerase II inhibitors and characteristically presents as overt t-AML with recurrent balanced chromosome aberrations. Recent research suggests that these 2 general types of t-AML can now be subdivided into at least 8 genetic pathways with a different etiology and different biologic characteristics.
BCR ligation reprograms B cells for migration to the T zone and B-cell follicle sequentially
Authors: Casamayor-Pallejà Montserrat , Mondière Paul , Verschelde Claire , Bella Chantal , Defrance Thierry 
Published: October 2002

AbstractWe have studied the impact of B-cell receptor (BCR) or CD40 ligation on the in vitro chemotactic response of tonsillar B cells to 4 chemokines: stromal cell–derived factor (SDF)–1α, macrophage inflammatory protein (MIP)–3α, MIP-3β, and B-cell–attracting chemokine (BCA)–1. In the tonsil, SDF-1 and MIP-3α are both expressed in the crypt epithelium, while MIP-3β is found in the T zone and BCA-1 in the follicles. Resting virgin and memory B cells display a similar chemotaxis pattern, and they both have the potential to migrate in vitro to all 4 chemokines studied. This pattern of responsiveness is strongly modified by a surrogate antigen (Ag) but is not altered by CD40 ligand. We report here that surrogate Ag induces a profound and sustained suppression of the response to the crypt chemokines SDF-1α and MIP-3α, while it exacerbates the migratory response to MIP-3β. The effect of surrogate Ag on the response to BCA-1 is biphasic: After an initial phase of suppression, chemotaxis toward BCA-1 is strongly up-regulated. Our results suggest that Ag is primarily responsible for reprogramming the B-cell chemotaxis responsiveness during the humoral response. We propose that it initiates an ordered change of the chemotaxis machinery allowing Ag-activated B cells to relocate in the T zone and B-cell follicles sequentially.
Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation
Authors: Weisdorf Daniel J. , Anasetti Claudio , Antin Joseph H. , Kernan Nancy A. , Kollman Craig , Snyder David , Petersdorf Effie , Nelson Gene , McGlave Philip 
Published: October 2002

AbstractAllogeneic bone marrow transplantation (BMT) offers the only curative therapy for chronic myelogenous leukemia. We compared prospectively collected results of 2464 unrelated donor (URD) transplantations with 450 HLA-identical, matched sibling donor (MSD) transplantations performed at collaborating National Marrow Donor Program institutions. A total of 63% of URDs were matched at HLA-A, -B, and at -DRB1 alleles; all MSDs were genotypically identical at major histocompatibility loci. URD recipients were younger (median 36 vs 39, P = .001) than MSDs and underwent BMT later after diagnosis (median 17 [0-325 months] vs 7 [1-118 months],P = .001) and less often in chronic phase (CP) (67% vs 82%, P = .001). Multivariate analysis demonstrated a significantly increased risk of graft failure and acute graft versus host disease after URD BMT. The risk of hematologic relapse was low after either matched URD or MSD transplantations. We observed significantly though modestly poorer survival and disease-free survival (DFS) after URD transplantations. However, for those undergoing transplantation during CP within 1 year from diagnosis, 5-year DFS was similar or only slightly inferior after matched URD versus MSD transplantation (age &lt; 30: URD 61% ± 8% vs MSD 68% ± 15%,P = .18; 30-40: URD 57% ± 9% vs MSD 67% ± 10%,P = .05; &gt; 40: URD 46% ± 9% vs MSD 57% ± 9%,P = .02). Delay from diagnosis to BMT in CP patients led to substantially poorer 5-year DFS after matched URD than MSD BMT (CP 1-2 years: URD 39% ± 6% vs MSD 63% ± 12%; beyond 2 years: URD 33% ± 7% vs MSD 50% ± 20%). Outcome of matched URD BMT for early CP chronic myelogenous leukemia yields survival and DFS approaching that of MSD transplantation. However, delay may compromise URD outcomes to a greater extent. Improvements in URD and MSD transplantation are still needed, and results of newer, nontransplantation therapies should be evaluated against the established curative potential of URD and MSD marrow transplantation.
Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor
Authors: De Marchis Francesco , Ribatti Domenico , Giampietri Claudia , Lentini Alessandro , Faraone Debora , Scoccianti Marco , Capogrossi Maurizio C. , Facchiano Antonio 
Published: October 2002

AbstractBasic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) modulate vascular wall cell function in vitro and angiogenesis in vivo. The aim of the current study was to determine how bovine aorta endothelial cells (BAECs) respond to the simultaneous exposure to PDGF-BB and bFGF. It was found that bFGF-dependent BAEC migration, proliferation, and differentiation into tubelike structures on reconstituted extracellular matrix (Matrigel) were inhibited by PDGF-BB. The role played by PDGF receptor α (PDGF-Rα) was investigated by selective stimulation with PDGF-AA, by blocking PDGF-BB-binding to PDGF-Rα with neomycin, or by transfecting cells with dominant-negative forms of the receptors to selectively impair either PDGF-Rα or PDGF-Rβ function. In all cases, PDGF-Rα impairment abolished the inhibitory effect of PDGF-BB on bFGF-directed BAEC migration. In addition, PDGF-Rα phosphorylation was increased in the presence of bFGF and PDGF, as compared to PDGF alone, whereas mitogen-activated protein kinase phosphorylation was decreased in the presence of PDGF-BB and bFGF compared with bFGF alone. In vivo experiments showed that PDGF-BB and PDGF-AA inhibited bFGF-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane assay and that PDGF-BB inhibited bFGF-induced angiogenesis in Matrigel plugs injected subcutaneously in CD1 mice. Taken together these results show that PDGF inhibits the angiogenic properties of bFGF in vitro and in vivo, likely through PDGF-Rα stimulation.
Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression
Authors: McLellan Alexander D. , Kapp Michaela , Eggert Andreas , Linden Christian , Bommhardt Ursula , Bröcker Eva-B. , Kämmerer Ulrike , Kämpgen Eckhart 
Published: October 2002

AbstractMouse spleen contains CD4+, CD8α+, and CD4−/CD8α− dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule–associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8α+ DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC subtypes stimulated allogeneic CD4+ T cells comparably. However, CD8α+ DCs were very weak stimulators of resting or activated allogeneic CD8+ T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8+ F5 T-cell receptor (TCR)–transgenic T cells. CD8α− or CD8α+DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I–peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8α DCs was responsible for the low allostimulatory capacity of CD8α+ DCs in vitro. Surprisingly, both CD8α+ DCs and CD4−/CD8− DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4+ DCs were weak inducers of CTLs. Thus, the inability of CD8α+ DCs to stimulate CD8+ T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo interaction between CD8α+ DCs and CD8+ T cells.
Interleukin-17 inhibits tumor cell growth by means of a T-cell–dependent mechanism
Authors: Benchetrit Fabrice , Ciree Arnaud , Vives Virginie , Warnier Guy , Gey Alain , Sautès-Fridman Catherine , Fossiez François , Haicheur Nacilla , Fridman Wolf H. , Tartour Eric 
Published: October 2002

AbstractInterleukin 17 (IL-17) is a proinflammatory cytokine produced by activated CD4+ memory T cells. We previously showed that IL-17 increased the growth rate of human cervical tumors transplanted into athymic nude mice. To address the possible role of T cells in the biologic activity of IL-17 for tumor control, we grafted 2 murine hematopoietic immunogenic tumors (P815 and J558L) transfected with a complementary DNA encoding murine IL-17 into syngeneic immunocompetent mice. We found that growth of the 2 IL-17–producing tumors was significantly inhibited compared with that of mock-transfected tumors. In contrast to the antitumor activity of IL-17 observed in immunocompetent mice, we observed no difference in the in vivo growth of IL-17–transfected or mock-transfected P815 cells (P815–IL-17 and P815-Neo, respectively) transplanted into nude mice. We then showed that IL-17 increased generation of specific cytolytic T lymphocytes (CTLs) directed against the immunodominant antigens from P815 called A, B, C, D, and E, since all mice injected with P815–IL-17 developed a P815-specific CTL response, whereas only 6 of 16 mice immunized with P815-Neo had a specific CTL response against the antigens. The induction of CTLs was associated with establishment of a tumor-protective immunity. These experiments suggest that T lymphocytes are involved in the antitumor activity of IL-17. Therefore, IL-17, like other cytokines, appears to be a pleiotropic cytokine with possible protumor or antitumor effects on tumor development, which often depends on the immunogenicity of tumor models.
The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression
Authors: Medina Francisco , Segundo Carmen , Campos-Caro Antonio , González-Garcı́a Inés , Brieva José A. 
Published: October 2002

AbstractPlasma cells (PCs) are the final B-cell differentiation stage. Recent evidence reveals relevant functional differences within the PC compartment. In rodents, early PCs formed in secondary lymphoid tissues show enhanced apoptosis and short life span, whereas PCs present in a final destination organ, such as the bone marrow (BM), have reached a stable prolonged survival state. BM PCs arrive at this organ as a circulating precursor whose cellular nature remains uncertain. An initial aim of this study was to characterize this circulating cell. We hypothesized that antibody-secreting cells detectable in the human blood after immunization might be a candidate precursor. These cells were obtained from the blood of volunteers immunized 6 days earlier with tetanus toxoid (tet), and they were unambiguously identified as PCs, as demonstrated by their expression of the CD38h phenotype, by morphology, by immunoglobulin (Ig) intracytoplasmic staining, and by IgG-tet–secreting capacity in vitro. In addition, by using the common CD38h feature, human PCs from tonsil (as a possible source of early PCs), from blood from tet-immunized donors (as the putative precursors of BM PCs), and from BM (as a deposit organ) have been purified and their phenotypes compared. The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyte-induced maturation protein 1 and B cell–specific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil→blood→BM. However, PCs from these different organs showed a local pattern of adhesion molecule expression. These observations are discussed in light of the complex physiology of the human PC compartment.
Comparison of anti-inflammatory and clinical effects of beclomethasone dipropionate and salmeterol in moderate asthma
Authors: Bacci E. , Di Franco A. , Bartoli M.L. , Carnevali S. , Cianchetti S. , Dente F.L. , Giannini D. , Vagaggini B. , Ruocco L. , Paggiaro P.L. 
Published: October 2002

Inhaled corticosteroids and long-acting β2‐agonists effectively control asthma symptoms and improve airway function. The effects of beclomethasone were compared with those of salmeterol on markers of eosinophilic inflammation in induced sputum in steroid-naïve asthmatic subjects with moderate asthma.Fifteen moderate asthmatics were treated with either beclomethasone dipropionate (500 µgb.i.d) or salmeterol (50 µgb.i.d) for 4 weeks, according to a randomised, double-blind, parallel-group study design. All patients underwent spirometry, methacholine test, sputum induction, and blood sampling before and after 2 and 4 weeks of treatment. They also recorded daily symptoms and peak expiratory flow (PEF).Sputum eosinophils, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), and blood eosinophils, as well as the forced expiratory volume in one second (FEV1) and morning PEF, significantly improved after beclomethasone but not after salmeterol. PEF variability, the symptom score and rescue β2‐agonist use significantly improved after both treatments, although the improvement in the symptom score tended to be greater after beclomethasone. After 2 and 4 weeks of beclomethasone treatment, both serum ECP and EPX decreased. With salmeterol, only serum EPX decreased, after 4 weeks. Bronchial hyperresponsiveness to methacholine did not change after either treatment.The authors conclude that beclomethasone, but not salmeterol, substantially improves airway inflammation in asthma. Beclomethasone also had an overall greater clinical effect, although the improvement in symptoms and peak expiratory flow variability was similar after both treatments.
Quality of life in patients with chronic alveolar hypoventilation
Authors: Dellborg C. , Olofson J. , Midgren B. , Caro O. , Skoogh B-E. , Sullivan M. 
Published: October 2002

Measurements of health-related quality of life (HRQL) have not been reported in patients with chronic alveolar hypoventilation (CAH) before starting home mechanical ventilation. The purpose of this study was to investigate quality of life in a population of such patients.Forty-four consecutive patients with CAH due to previous polio, scoliosis, healed pulmonary tuberculosis or neuromuscular disease answered a battery of condition specific and generic (Sickness Impact Profile, Hospital Anxiety and Depression scale, Mood Adjective Check List) self-report questionnaires. Spirometry, arterial blood gases and overnight oxygen saturation were measured.Patients with untreated CAH had significantly impaired HRQL compared to historical data from a healthy reference population. Sleep-related problems were frequent. Age, underlying disease, and standard bicarbonate correlated significantly with HRQL measures, albeit with modest levels of explained variance (8–37%).Patients with chronic alveolar hypoventilation due to neuromuscular or restrictive chest wall disorders had severely impaired health-related quality of life. Age, the underlying disease and severity of hypoventilation are each related to the health-related quality of life decrements. Health-related quality of life measurements add important information to traditional clinical observations.