bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Small Cell Lung Cancer Cells Induce Monocytes to Increase Expression of Angiogenic Activity
Authors: White Eric S. , Strom Scott R. B. , Wys Noel L. , Arenberg Douglas A. 
Published: April 2014

AbstractTumors are dependent on angiogenesis for survival and propagation. Accumulated evidence suggests that macrophages are a potentially important source of angiogenic factors in many disease states. However, the role(s) of macrophages in non-small cell lung cancer (NSCLC) have not been determined. We hypothesized that monocyte-derived macrophages are induced by NSCLC to increase expression of angiogenic factors. To define the role of macrophage-tumor cell interaction with respect to angiogenesis, human peripheral blood monocytes (PBM) were cocultured with A549 (human bronchoalveolar cell carcinoma) or Calu 6 (human anaplastic carcinoma) NSCLC cells. The resultant conditioned medium (CM) was evaluated for angiogenic potential and for expression of angiogenic factors. We found that endothelial cell chemotactic activity (as a measure of angiogenic potential) was significantly increased in response to CM from cocultures of PBM/NSCLC compared with PBM alone, NSCLC alone, or a combination of NSCLC and PBM CM generated separately. Subsequent analysis by ELISA reveals markedly increased CXC chemokine expression, with a lesser increase in vascular endothelial growth factor, in CM from PBM/NSCLC coculture. Neutralizing Ab to angiogenic CXC chemokines blocked the increase in endothelial cell chemotaxis. Furthermore, with separately generated CM as a stimulus, we found that macrophages are the predominant source of increased CXC chemokine expression. Finally, we found that NSCLC-derived macrophage migration-inhibitory factor is responsible for the increased expression of macrophage-derived angiogenic activity. These data suggest that the interaction between host macrophages and NSCLC cells synergistically increases angiogenic potential, and that this is due to an increased elaboration of angiogenic CXC chemokines.
Peripheral Blood Fibrocytes: Differentiation Pathway and Migration to Wound Sites
Authors: Abe Riichiro , Donnelly Seamas C. , Peng Tina , Bucala Richard , Metz Christine N. 
Published: April 2014

AbstractFibrocytes are a distinct population of blood-borne cells that display a unique cell surface phenotype (collagen I+/CD11b+/CD13+/CD34+/CD45RO+/MHC class II+/CD86+) and exhibit potent immunostimulatory activities. Circulating fibrocytes rapidly enter sites of tissue injury, suggesting an important role for these cells in wound repair. However, the regulatory processes that govern the differentiation of blood-borne fibrocytes and the mechanisms that underlie the migration of these cells to wound sites are currently not known. We report herein that ex vivo cultured fibrocytes can differentiate from a CD14+-enriched mononuclear cell population and that this process requires contact with T cells. Furthermore, we demonstrate that TGF-β1 (1–10 ng/ml), an important fibrogenic and growth-regulating cytokine involved in wound healing, increases the differentiation and functional activity of cultured fibrocytes. Because fibrocytes home to sites of tissue injury, we examined the role of chemokine/chemokine receptor interactions in fibrocyte trafficking. We show that secondary lymphoid chemokine, a ligand of the CCR7 chemokine receptor, acts as a potent stimulus for fibrocyte chemotaxis in vitro and for the homing of injected fibrocytes to sites of cutaneous tissue injury in vivo. Finally, we demonstrate that differentiated, cultured fibrocytes express α smooth muscle actin and contract collagen gels in vitro, two characteristic features of wound-healing myofibroblasts. These data provide important insight into the control of fibrocyte differentiation and trafficking during tissue repair and significantly expand their potential role during wound healing.
Ubiquitous Transgenic Expression of the IL-23 Subunit p19 Induces Multiorgan Inflammation, Runting, Infertility, and Premature Death
Authors: Wiekowski Maria T. , Leach Michael W. , Evans Ellen W. , Sullivan Lee , Chen Shu-Cheng , Vassileva Galya , Bazan J. Fernando , Gorman Daniel M. , Kastelein Robert A. , Narula Satwant , Lira Sergio A. 
Published: April 2014

Abstractp19, a molecule structurally related to IL-6, G-CSF, and the p35 subunit of IL-12, is a subunit of the recently discovered cytokine IL-23. Here we show that expression of p19 in multiple tissues of transgenic mice induced a striking phenotype characterized by runting, systemic inflammation, infertility, and death before 3 mo of age. Founder animals had infiltrates of lymphocytes and macrophages in skin, lung, liver, pancreas, and the digestive tract and were anemic. The serum concentrations of the proinflammatory cytokines TNF-α and IL-1 were elevated, and the number of circulating neutrophils was increased. In addition, ubiquitous expression of p19 resulted in constitutive expression of acute phase proteins in the liver. Surprisingly, liver-specific expression of p19 failed to reproduce any of these abnormalities, suggesting specific requirements for production of biologically active p19. Bone marrow transfer experiments showed that expression of p19 by hemopoietic cells alone recapitulated the phenotype induced by its widespread expression, pointing to hemopoietic cells as the source of biologically active p19. These findings indicate that p19 shares biological properties with IL-6, IL-12, and G-CSF and that cell-specific expression is required for its biological activity.
Eotaxin (CCL11) Induces In Vivo Angiogenic Responses by Human CCR3+ Endothelial Cells
Authors: Salcedo Rosalba , Young Howard A. , Ponce M. Lourdes , Ward Jerrold M. , Kleinman Hynda K. , Murphy William J. , Oppenheim Joost J. 
Published: April 2014

Abstract
Chemokines are attractants and regulators of cell activation. Several CXC family chemokine members induce angiogenesis and promote tumor growth. In contrast, the only CC chemokine, reported to play a direct role in angiogenesis is monocyte-chemotactic protein-1. Here we report that another CC chemokine, eotaxin (also known as CCL11), also induced chemotaxis of human microvascular endothelial cells. CCL11-induced chemotactic responses were comparable with those induced by monocyte-chemotactic protein-1 (CCL2), but lower than those induced by stroma-derived factor-1α (CXCL12) and IL-8 (CXCL8). The chemotactic activity was consistent with the expression of CCR3, the receptor for CCL11, on human microvascular endothelial cells and was inhibited by mAbs to either human CCL11 or human CCR3. CCL11 also induced the formation of blood vessels in vivo as assessed by the chick chorioallantoic membrane and Matrigel plug assays. The angiogenic response induced by CCL11 was about one-half of that induced by basic fibroblast factor, and it was accompanied by an inflammatory infiltrate, which consisted predominantly of eosinophils. Because the rat aortic sprouting assay, which is not infiltrated by eosinophils, yielded a positive response to CCL11, this angiogenic response appears to be direct and is not mediated by eosinophil products. This suggests that CCL11 may contribute to angiogenesis in conditions characterized by increased CCL11 production and eosinophil infiltration such as Hodgkin’s lymphoma, nasal polyposis, endometriosis, and allergic diathesis.
Myelin Antigen-Specific CD8+ T Cells Are Encephalitogenic and Produce Severe Disease in C57BL/6 Mice
Authors: Sun Deming , Whitaker John N. , Huang Zhigang , Liu Di , Coleclough Christopher , Wekerle Hartmut , Raine Cedric S. 
Published: April 2014

AbstractEncephalitogenic T cells that mediate experimental autoimmune encephalomyelitis (EAE) are commonly assumed to be exclusively CD4+, but formal proof is still lacking. In this study, we report that synthetic peptides 35–55 from myelin oligodendrocyte glycoprotein (pMOG35–55) consistently activate a high proportion of CD8+ αβTCR+ T cells that are encephalitogenic in C57BL/6 (B6) mice. The encephalitogenic potential of CD8+ MOG-specific T cells was established by adoptive transfer of CD8-enriched MOG-specific T cells. These cells induced a much more severe and permanent disease than disease actively induced by immunization with pMOG35–55. CNS lesions in pMOG35–55 CD8+ T cell-induced EAE were progressive and more destructive. The CD8+ T cells were strongly pathogenic in syngeneic B6 and RAG-1−/− mice, but not in isogeneic β2-microglobulin-deficient mice. MOG-specific CD8+ T cells could be repeatedly reisolated for up to 287 days from recipient B6 or RAG-1−/− mice in which disease was induced adoptively with &lt;1 × 106 T cells sensitized to pMOG35–55. It is postulated that MOG induces a relapsing and/or progressive pattern of EAE by eliciting a T cell response dominated by CD8+ autoreactive T cells. Such cells appear to have an enhanced tissue-damaging effect and persist in the animal for long periods.
MHC Class II-Regulated Central Nervous System Autoaggression and T Cell Responses in Peripheral Lymphoid Tissues Are Dissociated in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis
Authors: Weissert Robert , de Graaf Katrien L. , Storch Maria K. , Barth Silvia , Linington Christopher , Lassmann Hans , Olsson Tomas 
Published: April 2014

AbstractWe dissected the requirements for disease induction of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis in MHC (RT1 in rat) congenic rats with overlapping MOG peptides. Immunodominance with regard to peptide-specific T cell responses was purely MHC class II dependent, varied between different MHC haplotypes, and was linked to encephalitogenicity only in RT1.Ba/Da rats. Peptides derived from the MOG sequence 91–114 were able to induce overt clinical signs of disease accompanied by demyelinated CNS lesions in the RT1.Ba/Da and RT1n haplotypes. Notably, there was no detectable T cell response against this encephalitogenic MOG sequence in the RT1n haplotype in peripheral lymphoid tissue. However, CNS-infiltrating lymphoid cells displayed high IFN-γ, TNF-α, and IL-4 mRNA expression suggesting a localization of peptide-specific reactivated T cells in this compartment. Despite the presence of MOG-specific T and B cell responses, no disease could be induced in resistant RT1l and RT1u haplotypes. Comparison of the number of different MOG peptides binding to MHC class II molecules from the different RT1 haplotypes suggested that susceptibility to MOG-experimental autoimmune encephalomyelitis correlated with promiscuous peptide binding to RT1.B and RT1.D molecules. This may suggest possibilities for a broader repertoire of peptide-specific T cells to participate in disease induction. We demonstrate a powerful MHC class II regulation of autoaggression in which MHC class II peptide binding and peripheral T cell immunodominance fail to predict autoantigenic peptides relevant for an autoaggressive response. Instead, target organ responses may be decisive and should be further explored.
Protein Kinase A RIβ Subunit Deficiency in Lupus T Lymphocytes: Bypassing a Block in RIβ Translation Reconstitutes Protein Kinase A Activity and Augments IL-2 Production
Authors: Khan Islam U. , Laxminarayana Dama , Kammer Gary M. 
Published: April 2014

Abstract
A profound deficiency of type I protein kinase A (PKA-I or RIα/β2C2) phosphotransferase activity occurs in the T lymphocytes of 80% of subjects with systemic lupus erythematosus (SLE), an autoimmune disorder of unknown etiology. This isozyme deficiency is predominantly the product of reduced or absent β isoform of the type I regulatory subunit (RIβ). Transient transfection of RIβ cDNAs from SLE subjects into autologous T cells that do not synthesize the RIβ subunit bypassed the block, resulting in RIβ subunit synthesis and restoration of the PKA-Iβ (RIβ2C2) holoenzyme. Transfected T cells activated via the T cell surface receptor complex revealed a significant increase of cAMP-activatable PKA activity that was associated with a significant increase in IL-2 production. These data demonstrate that a disorder of RIβ translation exists, and that correction of the PKA-I deficiency may enhance T lymphocyte effector functions in SLE.
Antibodies to C-C Chemokine Receptor 5 in Normal Human IgG Block Infection of Macrophages and Lymphocytes with Primary R5-Tropic Strains of HIV-1
Authors: Bouhlal Hicham , Hocini Hakim , Quillent-Grégoire Caroline , Donkova Vladimira , Rose Stephanie , Amara Ali , Longhi Renato , Haeffner-Cavaillon Nicole , Beretta Alberto , Kaveri Srini V. , Kazatchkine Michel D. 
Published: April 2014

Abstract
In the present study, we demonstrate that normal human IgG for therapeutic use (i.v. Ig) contains natural Abs directed against the CCR5 coreceptor for HIV-1. Abs to CCR5 were isolated from i.v. Ig using an affinity matrix consisting of a synthetic peptide corresponding to the N-terminus of CCR5 coupled to Sepharose. Natural anti-CCR5 Abs inhibited the binding of RANTES to macrophages, demonstrating their interaction with the coreceptor of R5-tropic HIV-1. Affinity-purified anti-CCR5 Ig further inhibited infection of lymphocytes and monocytes/macrophages with primary and laboratory-adapted strains of HIV-1, but did not inhibit infection with X4-tropic HIV. Our results suggest that anti-CCR5 Abs from healthy immunocompetent donors may be suitable for development of novel passive immunotherapy regimens in specific clinical settings in HIV infection.
Molecular Basis of a Selective C1s Deficiency Associated with Early Onset Multiple Autoimmune Diseases
Authors: Dragon-Durey Marie-Agnès , Quartier Pierre , Frémeaux-Bacchi Véronique , Blouin Jacques , de Barace Claire , Prieur Anne-Marie , Weiss Laurence , Fridman Wolf-Herman 
Published: April 2014

AbstractWe have investigated the molecular basis of selective and complete C1s deficiency in 2-year-old girl with complex autoimmune diseases including lupus-like syndrome, Hashimoto’s thyroiditis, and autoimmune hepatitis. This patient’s complement profile was characterized by the absence of CH50 activity, C1 functional activity &lt;10%, and undetectable levels of C1s Ag associated with normal levels of C1r and C1q Ags. Exon-specific amplification of genomic DNA by PCR followed by direct sequence analysis revealed a homozygous nonsense mutation in the C1s gene exon XII at codon 534, caused by a nucleotide substitution from C (CGA for arginine) to T (TGA for stop codon). Both parents were heterozygous for this mutation. We used the new restriction site for endonuclease Fok-1 created by the mutation to detect this mutation in the genomic DNA of seven healthy family members. Four additional heterozygotes for the mutation were identified in two generations. Our data characterize for the first time the genetic defect of a selective and complete C1s deficiency in a Caucasian patient.
CXCL10 (IFN-γ-Inducible Protein-10) Control of Encephalitogenic CD4+ T Cell Accumulation in the Central Nervous System During Experimental Autoimmune Encephalomyelitis
Authors: Fife Brian T. , Kennedy Kevin J. , Paniagua Mary C. , Lukacs Nicholas W. , Kunkel Steven L. , Luster Andrew D. , Karpus William J. 
Published: April 2014

AbstractExperimental autoimmune encephalomyelitis (EAE) is a CD4+ Th1-mediated demyelinating disease of the CNS that serves as a model for multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific and Ag-nonspecific T lymphocytes into the CNS. In the present report, we investigated the role of the CXC chemokine CXCL10 (IFN-γ-inducible protein-10) in the pathogenesis of EAE. Production of CXCL10 in the CNS correlated with the development of clinical disease. Administration of anti-CXCL10 decreased clinical and histological disease incidence, severity, as well as infiltration of mononuclear cells into the CNS. Anti-CXCL10 specifically decreased the accumulation of encephalitogenic PLP139–151 Ag-specific CD4+ T cells in the CNS compared with control-treated animals. Anti-CXCL10 administration did not affect the activation of encephalitogenic T cells as measured by Ag-specific proliferation and the ability to adoptively transfer EAE. These results demonstrate an important role for the CXC chemokine CXCL10 in the recruitment and accumulation of inflammatory mononuclear cells during the pathogenesis of EAE.
The Prevention and Treatment of Murine Colitis Using Gene Therapy with Adenoviral Vectors Encoding IL-10
Authors: Lindsay James O. , Ciesielski Cathleen J. , Scheinin Tom , Hodgson Humphrey J. , Brennan Fionula M. 
Published: April 2014

AbstractIL-10-deficient (IL-10−/−) mice develop colitis with many similarities to Crohn’s disease. Daily IL-10 injections have a short systemic half-life and are unable to induce complete remission in IL-10−/− mice with established disease. In this paper, we investigate the duration, potency, and immunogenicity of gene therapy using an adenoviral vector encoding murine IL-10 (AdvmuIL-10). A single systemic injection of AdvmuIL-10 was sufficient not only to prevent the onset of colitis for at least 10 wk but also to induce clinical and histological remission in mice with established disease. In addition, AdvmuIL-10 diminished the systemic manifestations of disease, including elevated acute-phase proteins, as well as the local consequences of inflammation such as raised stool IL-1β concentrations. Both IL-10 protein and the effects of secreted IL-10 were detectable for 10 wk after AdvmuIL-10 injection. Furthermore, the immunoregulatory effect of a single AdvmuIL-10 injection was manifest both by a reduction in TNF-α, IFN-γ, and RANTES release from stimulated splenocyte cultures, and also by a change in the proportion of CD45RBhigh/low lymphocytes in the spleen compared with control mice. The delivery of AdvmuIL-10 resulted in a significantly diminished host antiadenoviral response compared with control adenoviral vectors. Thus, gene therapy strategies using adenoviral vectors encoding immunoregulatory and antiinflammatory cytokines may prove to be a potent approach for the treatment of chronic inflammatory disease. Antiinflammatory cytokine expression protects against immune responses directed at gene vectors.
Ex Vivo IFN-γ Secretion by Circulating CD8 T Lymphocytes: Implications of a Novel Approach for T Cell Monitoring in Infectious and Malignant Diseases
Authors: Pittet Mikaël J. , Zippelius Alfred , Speiser Daniel E. , Assenmacher Mario , Guillaume Philippe , Valmori Danila , Liénard Danielle , Lejeune Ferdy , Cerottini Jean-Charles , Romero Pedro 
Published: April 2014

AbstractTo elucidate the functional heterogeneity of Ag-specific T lymphocyte populations, we combined labeling of lymphocytes with MHC/peptide tetramers and a cell surface affinity matrix for IFN-γ. Magnetic cell sorting of IFN-γ-positive lymphocytes allowed the selective enrichment and identification of live Ag-specific cytokine-secreting cells by flow cytometry. Naive, memory, and effector Ag-specific populations were evaluated in healthy HLA-A2 individuals. Significant fractions of influenza- and CMV-specific cells secreted IFN-γ upon challenge with cognate peptide, consistent with an effector/memory status. The sensitivity of the approach allowed the detection of significant numbers of CMV-specific IFN-γ-secreting cells ex vivo (i.e., without Ag stimulation). This was not apparent when using previously described assays, namely, ELISPOT or intracellular IFN-γ staining (cytospot). CD8+ T cells specific for the melamoma-associated Ag Melan-A/MART-1 did not produce IFN-γ upon challenge with cognate peptide, reminiscent with their naive functional state in healthy individuals. In contrast, CD45RAlow Melan-A/MART-1 tumor-specific cells from three of three melanoma patients presented levels of activity similar to those found for influenza- or CMV virus-specific lymphocytes, compatible with a functional differentiation into competent effector/memory T lymphocytes in vivo. Notably, a sizable fraction of Melan-A/MART-1-specific cells from a patient secreted IFN-γ ex vivo following peptide-based vaccination. Thus, the high sensitivity of the assay provides a valuable tool to monitor effector T cell responses in different clinical situations.
Cutting Edge: CD43 Functions as a T Cell Counterreceptor for the Macrophage Adhesion Receptor Sialoadhesin (Siglec-1)
Authors: van den Berg Timo K. , Nath Deepa , Ziltener Hermann J. , Vestweber Dietmar , Fukuda Minoru , van Die Irma , Crocker Paul R. 
Published: April 2014

AbstractSialoadhesin (Siglec-1) is a macrophage-restricted sialic acid-binding receptor that mediates interactions with hemopoietic cells, including lymphocytes. In this study, we identify sialoadhesin counterreceptors on T lymphocytes. Several major glycoproteins (85, 130, 240 kDa) were precipitated by sialoadhesin-Fc fusion proteins from a murine T cell line (TK-1). Binding of sialoadhesin to these glycoproteins was sialic acid dependent and was abolished by mutation of a critical residue (R97A) of the sialic acid binding site in the membrane distal Ig-like domain of sialoadhesin. The 130- and 240-kDa sialoadhesin-binding glycoproteins were identified as the sialomucins CD43 and P-selectin glycoprotein ligand 1 (CD162), respectively. CD43 expressed in COS cells supported increased binding to immobilized sialoadhesin. Finally, sialoadhesin bound different glycoforms of CD43 expressed in Chinese hamster ovary cells, including unbranched (core 1) and branched (core 2) O-linked glycans, that are normally found on CD43 in resting and activated T cells, respectively. These results identify CD43 as a T cell counterreceptor for sialoadhesin and suggest that in addition to its anti-adhesive role CD43 may promote cell-cell interactions.
Cutting Edge: Regulation of Uterine NKT Cells by a Fetal Class I Molecule Other Than CD1
Authors: Dang Yushe , Heyborne Kent D. 
Published: April 2014

AbstractThe peri-implantation uterus contains an expanded population of NK1.1+ Vα14+ TCRint (NKT) lymphocytes. Although these cells bear the above features in common with other NKT cells populations in thymus, bone marrow, liver, and spleen, they differ from these other populations in terms of an altered Vβ repertoire and absence of a CD4+ component. In this study, we demonstrate that the uterine population also differs from other NKT cell populations because they recognize a class I/class I-like molecule other than CD1, whereas most previously described Vα14+ NKT cells are CD1-restricted. Moreover, the class I/class I-like molecule leading to the uterine NKT cell expansion may be supplied by the fetus. These data demonstrate a novel mechanism whereby the fetus is capable of modulating the maternal immune system.
Cutting Edge: CTLs Rapidly Capture Membrane Fragments from Target Cells in a TCR Signaling-Dependent Manner
Authors: Hudrisier Denis , Riond Joelle , Mazarguil Honoré , Gairin Jean Edouard , Joly Etienne 
Published: April 2014

Abstract
Upon encounter of a CTL with a target cell carrying foreign Ags, the TCR internalizes with its ligand, the peptide-MHC class I complex. However, it is unclear how this can happen mechanistically because MHC molecules are anchored to the target cell’s surface via a transmembrane domain. By using antigenic peptides and lipids that were fluorescently labeled, we found that CTLs promptly capture target cell membranes together with the antigenic peptide as well as various other surface proteins. This efficient and specific capture process requires sustained TCR signaling. Our observations indicate that this process allows efficient acquisition of the Ag by CTL, which may in turn regulate lymphocyte activation or elimination.