bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD40 can costimulate human memory T cells and favors IL‐10 secretion
Authors: Rogers Nicola Jane , Jackson Ian Michael , Jordan William James , Lombardi Giovanna , Delikouras Alexandros , Lechler Robert Ian 
Published: March 2003

AbstractOptimal proliferation of T cells, although initiated via ligation of the CD3/TCR complex, requires additional costimulatory signals. While the most well‐defined in vitro pathway of costimulation is via the B7 family of molecules, a large body of data clearly demonstrates an in vivo role for the CD40/CD154 pathway in transplantation, autoimmunity and allergy. We have examined the role of CD40 as an independent costimulatory molecule by generating a panel of transfected human fibroblasts expressing DR1 with either CD80, CD86 or CD40. Functional assays using allogeneic CD4+ T cells as responders demonstrated that CD40 was capable of costimulating CD4+ T cell proliferation particularly in the CD45RO subset. Costimulation by CD40 induced much higher levels of IL‐10 than were induced by B7‐expressing cells. On day 3 the dominant costimulation was provided by CD40, while by day 5 this was overshadowed by CD80 and CD86. Nonetheless, the provision of costimulation by CD40 was enough to expand an alloreactive T cell line. These results were confirmed in experiments using primary cultures of CD40+CD80/CD86– renal tubular epithelial cells as the stimulator population. Thus, CD40 is capable of functioning independently (in the absence of B7) as a costimulatory molecule both in terms of proliferation and cytokine release. The data have interesting implications concerning the consequences of antigen presentation by tissue parenchymal cells.
Colonic lamina propria dendritic cells in mice with CD4+ T cell‐induced colitis
Authors: Krajina Tamara , Leithäuser Frank , Möller Peter , Trobonjaca Zlatko , Reimann Jörg 
Published: March 2003

AbstractCD11c+ (F4/80– CD68–) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1–/–) C57BL/6 (B6) mice show high surface expression of MHC class I/II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4+ α β T cells from normal or MHC class II‐deficient B6 micetransferred into congenic RAG1–/– hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up‐regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non‐transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL‐12 p70 and IL‐10 in response to CD40 signaling, but the inducible IL‐12 p40 release is 5–15‐fold higher in mice with colitis than in non‐transplanted mice. Binding of IL‐12 p40 to p19 generates IL‐23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3–10‐fold more p19 transcripts than cLPL from non‐transplanted, healthy mice. p19 expression by cLPL is further up‐regulated in response to CD40 ligation. Freshly isolated cLP DC from transplanted mice with colitis (but not from non‐transplanted controls) stimulate IFN‐γ (but not IL‐4 or IL‐13) release by co‐cultured NKT cells. Incolitis, DC accumulate in the cLP, show an activated surface phenotype, up‐regulate IL‐12 p40 and p19 expression, and ‘spontaneously’ stimulate NKT‐like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.
Murine thymic plasmacytoid dendritic cells
Authors: Okada Tomoyuki , Lian Zhe‐Xiong , Naiki Mitsuru , Ansari Aftab A. , Ikehara Susumu , Gershwin M. Eric 
Published: March 2003

AbstractWe report herein heterogeneous murine thymic cell subsets expressing CD11c and B220 (CD45R). The CD11c+B220+ subset expresses Ly6Chigh and MHC class IIlow in contrast with previously described thymic DC (CD11c+B220– cells). Freshly isolated thymic CD11c+B220+ cells show typical plasmacytoid morphology which differentiates to mature DC, in vitro with CpG oligodeoxynucleotides (ODN) 2216; we term this subset thymic plasmacytoid DC (pDC). These thymic pDC are highly sensitive to spontaneous apoptosis in vitro and induce low T cell allo‐proliferation activity. Thymic pDC express low TLR2, TLR3 and TLR4 mRNA, normally found on human immature DC, and high TLR7 and TLR9 mRNA, normally found on human pDC. Thymic pDC also produce high amounts of IFN‐α following culture with CpG ODN 2216 (TLR9 ligands) as compared with the previously defined thymic DC lineage which expresses low TLR9 mRNA and produce high IL‐12 (p40) with CpG ODN 2216. These results indicate that thymic pDC are similar to IFN‐producing cells as well as human pDC. The TLR and cytokine production profiles are consistent with a nomenclature of pDC. The repertoire of this cell lineage to TLR9 ligands demonstrate that such responses are determined not only by the quantity of expression, but also cell lineage.
IFN‐γ‐mediated inhibition of antigen receptor‐induced B cell proliferation and CREB‐1 binding activity requires STAT‐1 transcription factor
Authors: Frissora Frank , Chen Hui‐Chen , Durbin Joan , Bondada Subbarao , Muthusamy Natarajan 
Published: March 2003

AbstractWe report here a role for cyclic AMP‐responsive element‐binding protein‐1 (CREB‐1) in B cell antigen receptor (BCR)‐induced growth inhibition by IFN‐γ. BCR‐induced proliferation is negatively regulated by IFN‐γ. Stimulation through BCR resulted in dose‐dependent induction of CREB‐1 binding to the consensus cyclic AMP‐responsive element. Recombinant IFN‐γ inhibited the BCR‐induced CREB‐1 DNA binding activity and cell proliferation in B cells from signal transducer and activator of transcription‐1 (STAT‐1)+/+, but not STAT‐1–/– mice. These studies provide the first evidence for cross‐talk between the STAT‐1 and CREB‐1 signaling pathways in IFN‐γ‐mediated negative regulation of B cell activation.
Plasmacytoid dendritic cells prime IFN‐γ‐secreting melanoma‐specific CD8 lymphocytes and are found in primary melanoma lesions
Authors: Salio Mariolina , Cella Marina , Vermi William , Facchetti Fabio , Palmowski Michael J. , Smith Caroline L. , Shepherd Dawn , Colonna Marco , Cerundolo Vincenzo 
Published: March 2003

AbstractPlasmacytoid dendritic cells (PDC) are a small population of leukocytes specialized in the production of type I IFN. It has been shown that PDC have a potent T cell stimulatory capacity in allogeneic mixed lymphocyte reaction, However, their role in initiating primary immune responses remains elusive. We report that blood PDC efficiently prime naive CD8+ lymphocytes specific forthe melan‐A26–35 epitope to become IFN‐γ producing cells in vitro. In addition, we found that CD40L‐stimulated PDC induce expression on primed melan‐A‐specific T cells of cutaneous lymphocyte antigen and L‐selectin (CD62L), homing receptors that allow the migration of effector cells to the inflamed skin. Finally, we show that PDC can be found in the peri‐tumoralarea of most primary cutaneous melanomas in vivo and that type I IFN‐containing supernatants derived from PDC increase melanoma cell surface expression of CD95 and MHC class I and class II molecules in vitro. Our results suggest a new immunomodulatory role for tissue infiltrating PDC, which may prime tumor‐specific T cell responses and affect tumor growth via soluble factors.
Natural killer cell receptors in cattle: a bovine killer cell immunoglobulin‐like receptor multigene family contains members with divergent signaling motifs
Authors: Storset Anne K. , Slettedal Imer Ö. , Williams John L. , Law Andy , Dissen Erik 
Published: March 2003

AbstractNatural killer (NK) cells recognize and kill certain tumor cells, virally infected cells and MHC class I‐disparate normal hematopoietic cells. NK cell cytotoxicity is regulated by a multitude of receptors with either activating or inhibitory signaling function. We here report the molecular cloning of bovine CD94 [killer cell lectin‐like receptor (KLR)‐D1] and NKp46 orthologues, four members of a bovine CD158 [killer cell immunoglobulin‐like receptor (KIR)] family, and a novel KLR. This novel receptor was termed KLRJ1 and is most similar to Ly‐49 (KLRA). The KLRD1 and KLRJ1 loci were mapped to a bovine NK gene complex on chromosome 5 by radiation hybrid mapping, whereas KIR2DL1 and NKP46 were localized to chromosome 18. Two of the bovine KIR(KIR2DL1 and KIR3DL1) contain immunoreceptor tyrosine‐based inhibition motifs (ITIM), suggesting an inhibitory function. Bovine KIR2DS1 and KIR3DS1 lack ITIM but have an arginine‐containing motif in their transmembrane domain, similar to primate KIR2DL4. Thus, KIR multigene families with divergent signaling motifs do not only exist in primates. Based on sequence comparison, it appears that the primate and bovine KIR multigene families may have evolved independently.
The IL‐1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model
Authors: Schmitz Nicole , Kurrer Michael , Kopf Manfred 
Published: March 2003

AbstractIL‐1α and IL‐1β are potent pro‐inflammatory cytokines that regulate many physiological systems by binding and signaling to the same receptor termed IL‐1 receptor type 1 (IL‐1R1). We have investigated the role of IL‐1 for pulmonary immune responses in models of allergic asthma using IL‐1R1‐deficient (IL‐1R1–/–) mice. In a model of mild asthma, based on repeated sensitization of mice with low doses of ovalbumin in the absence of any adjuvant and multiple intranasal challenges, the pulmonary eosinophilic inflammation and goblet cell hyperplasia were strongly reduced in IL‐1R1–/– as compared to control BALB/c mice. Moreover, priming of CD4+ T cells in bronchial lymph nodes and their recruitment to the lung was affected in IL‐1R1–/– miceassociated with impaired antibody responses including IgG, IgE, and IgA. In contrast, sensitization of mice in the presence of alum adjuvant, a more severe asthma model, rendered the IL‐1 pathway dispensable for the development of pulmonary allergic Th2 responses, as eosinophilic inflammation, antibody responses, and CD4+ T cell priming in lymph nodes were comparable between IL‐1R1–/– and wild‐type mice. These results suggest a critical role of IL‐1/IL‐1R1 for development of allergic Th2 responses, but its requirement can be overcome by using alum as adjuvant for sensitization.
Cooperation between toll‐like receptor 2 and 4 in the brain of mice challenged with cell wall components derived from gram‐negative and gram‐positive bacteria
Authors: Laflamme Nathalie , Echchannaoui Hakim , Landmann Régine , Rivest Serge 
Published: March 2003

AbstractIn this study we investigated whether induction of toll‐like receptor 2 (TLR2) amplifies the effect of a cell wall component derived from gram‐positive bacteria, namely peptidoglycan (PGN). Mice received a first systemic lipopolysaccharide (LPS) injection to pre‐induce TLR2 in various regions of the brain, and 6 h later, a second administration of either LPS or PGN. The data show a robust transcriptional activation of TLR2, TNF‐α and monocyte chemotactic protein‐1 (MCP‐1) in microglial cells of mice challenged twice with LPS, whereas PGN essentially abolished this response. TLR4 plays a critical role in this process, because C3H/HeJ mice no longer responded to LPS but exhibited a normal reaction to PGN. Conversely, a robust signal for genes encoding innate immune proteinswas found in the brain of TLR2‐deficient mice challenged with LPS. However, the second LPS bolus failed to trigger TNF‐α and IL‐12 in TLR2‐deficient mice, while the same treatment caused a strong induction of these genes in the cerebral tissue of wild‐type littermates. The present data provide evidence that cooperation exists between TLR4 and TLR2. While TLR4 is absolutely necessary to engage the innate immune response in the brain, TLR2 participates in the regulation of genes encoding TNF‐α and IL‐12 during severe endotoxemia. Such collaboration between TLR4 and TLR2 may be determinant for the transfer from the innate to the adaptive immunity within the CNS of infected animals.
Toll‐like receptor 2 (TLR2) and TLR4 differentially activate human mast cells
Authors: Varadaradjalou Sonia , Féger Frédéric , Thieblemont Nathalie , Hamouda Nadine Ben , Pleau Jean‐Marie , Dy Michel , Arock Michel 
Published: March 2003

AbstractIn the present report we have analyzed whether human normal cord blood‐derived mast cells (CBMC) could interact with bacterial products, especially lipopolysaccharide (LPS) from Escherichia coli and peptidoglycan (PGN) from Staphylococcus aureus, known as Toll‐like receptor (TLR) 4 and TLR2 agonists, respectively. We found that both LPS and PGN induced significant release of not only tumor necrosis factor‐α (TNF‐α), but also IL‐5, IL‐10 and IL‐13 by human mast cells (MC). We also established that the stimulation of CBMC with LPS or with PGN is mediated through interactions with TLR4 or with TLR2, respectively. Thus, our data indicate that activation of either TLR2 or TLR4 pathway may lead to a pro‐Th2 immune response. However, the release of TNF‐α induced by LPS, conversely to PGN, required the priming of CBMC by IL‐4 and the presence of serum components, in particular soluble CD14. Of interest, stimulation by PGN, but not by LPS, induced release of histamine by human MC. Altogether, these findings provide the first evidence that human MC differentially respond towards bacterial components, and that their responses depend on TLR pathways and reveal human specificities in the pattern of cytokine production.
Kinetics and STAT4‐ or STAT6‐mediated regulation of genes involved in lymphocyte polarization to Th1 and Th2 cells
Authors: Lund Riikka J. , Ylikoski Emmi K. , Aittokallio Tero , Nevalainen Olli , Lahesmaa Riitta 
Published: March 2003

AbstractMany genes implicated in Th1 and Th2 differentiation have been identified in both human and mouse. However, the functional roles and hierarchy of these factors in the signaling pathways leading to either Th1 or Th2 responses are less clear. To explore at which stage of polarization the differences between Th1 and Th2 cells occur, we have studied the expression of 23 key genes implicated in the process during the first week of polarization from human precursor T helper cells using quantitative real‐time reverse transcription‐PCR. According to our results, 14 of the genes were clearly regulated differentially in Th1 and Th2 conditions in distinct time‐dependent patterns, either during the first 2 days or after 1 week of polarization. Furthermore, 6 of these genes were identified to be targets of STAT4/6 regulation. Thus, for the first time we demonstrate expression kinetics of a number of key genes involved in Th1 and Th2 differentiation during the first week of polarization in both human and mouse. In addition, our study shows for the first time that the genes BCL‐6 and TRADD are differentially regulated during the polarization of human Th1 and Th2 cells.
Enantioselective Recognition of Aliphatic Amino Acids by β‐Cyclodextrin Derivatives Bearing Aromatic Organoselenium Moieties on the Primary or Secondary Side
Authors: Liu Yu , You Chang‐Cheng , Zhang Heng‐Yi , Zhao Yan‐Li 
Published: March 2003

AbstractSpectrophotometric titrations have been performed in order to determine the stability constants of inclusion complexation of some aliphatic amino acids with four structurally related organoselenium‐modified β‐cyclodextrins: mono(6‐phenylseleno‐6‐deoxy)‐β‐cyclodextrin (1a), mono[6‐(p‐methoxyphenylseleno)‐6‐deoxy]‐β‐cyclodextrin (1b), mono(2‐phenylseleno‐2‐deoxy)‐β‐cyclodextrin (2a), and mono[2‐(p‐methoxyphenylseleno)‐2‐deoxy]‐β‐cyclodextrin (2b). Conformation analysis by circular dichroism and 2D NMR spectroscopic studies revealed that the aryl‐substituted β‐cyclodextrins gave self‐inclusion intramolecular complexes in aqueous solution, while the extent of penetration depended both on the positions and on the structures of substituents. Quantitative investigation on the binding ability of the hosts with amino acids showed that they were able to recognize the size and the shape of guests, affording supramolecular complexes with quite small stability constants ranging from 24 to 355 M−1. The molecular recognition abilities are discussed from the viewpoints of induced‐fitting mechanisms, geometric complementary, and cooperative binding processes. Furthermore, these β‐cyclodextrin derivatives displayed considerable enantioselectivity towards L/D‐amino acid isomers, giving the highest L‐enantioselectivity (up to 8.4) for inclusion complexation between leucine and 2a. The binding modes of L/D‐leucine with 1b were elucidated from NOESY studies and the chiral recognition phenomena were interpreted accordingly. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Access to Isolable Azomethine Ylides by Photochemical Transformation of 2,3‐Dihydroisoxazoles
Authors: Lopez‐Calle Eloisa , Keller Manfred , Eberbach Wolfgang 
Published: March 2003

AbstractPhotochemical excitation of the 2,3‐dihydroisoxazoles 19−21 resulted in the formation of the stable azomethine ylides 22, 25, and 28, representing the first isolable examples of such species bearing stabilizing groups only at one end of the 1,3‐dipole. The UV and NMR spectroscopic data of the photoproducts clearly indicate that the iminium and the anionic parts of the azomethine ylide systems are not planar. This conclusion is unambiguously confirmed by crystal structure analysis of 25b, in which a twist angle of 73° was determined between the two polar moieties. In the case of 25d the rotation barrier around the central CN bond amounts to 16 kcal/mol at 333 K. In line with the unusual stability of the ylides is their low reactivity against dipolarophiles. Only the highly reactive N‐methyltriazolidinedione gives formation of the products 33a, 35a−c, and 41, but these are the result not of an initial 1,3‐dipolar cycloaddition but rather of a formal [4+2] addition with involvement of 34a, 36a−c, and 41 as unstable primary products. On heating in refluxing toluene the azomethine ylides are transformed into annulated pyrrole systems (42/43, 46/47, 48/49). In contrast to other examples, the direct thermal transformation of the annulated 2,3‐dihydroisoxazoles into pyrroles is not successful, but the reaction can be achieved by simultaneous thermal and photochemical activation, as shown for the conversion of 19 into the pyrroles 42/43. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Substituent Effects in the Vinylcyclopropane Radical Cation Rearrangement: A Computational Road to a New Synthetic Tool
Authors: Oxgaard Jonas , Wiest Olaf 
Published: March 2003

AbstractThe effect of substituents on the rearrangement of vinylcyclopropane radical cation to cyclopentene was explored by density functional theory. Correlations have been established between the activation energy of the system and the nature, as well as the position, of the substituents. It was found that radical‐ or cation‐stabilizing substituents in select positions reduce the activation energy for the rearrangement substantially, while activation energies for competing hydrogen shifts were largely left unchanged. We have identified positions in the vinylcyclopropane where substitution is necessary, and others that can be substituted less discriminately. The mechanism of the rearrangement changes from stepwise to concerted when a strongly cation‐stabilizing substituent is used, because the first step in the stepwise reaction becomes a barrierless ring opening of a strained cyclopropane. Steric effects were also explored and have been found to be of crucial importance for the success of a rearrangement. Finally, a simple set of rules has been devised to predict the outcome of oxidation of a vinylcyclopropane without requiring detailed mechanistic investigations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Quinoline‐Containing Calixarene Fluoroionophores: A Combined NMR, Photophysical and Modeling Study
Authors: Casnati Alessandro , Sansone Francesco , Sartori Andrea , Prodi Luca , Montalti Marco , Zaccheroni Nelsi , Ugozzoli Franco , Ungaro Rocco 
Published: March 2003

AbstractThe 8‐alkoxy‐5‐chloroquinoline fluorophore was appended at the lower rim of a calix[4]arene triamide with two different orientations. In ligand1the quinoline part is linked to the calixarene skeleton through the pyridine C2atom, while in2it is linked through the phenolic oxygen atom of the chromophore. The binding properties of both ligands, investigated in chloroform and methanol solutions, indicate that they are efficient fluoroionophores, with selectivity for sodium and strontium ions among alkali and alkaline earth metal ions. Combined NMR, photophysical, and modeling studies disclosed the peculiar conformational and coordination features of monovalent and divalent metal ion complexes. Lanthanide metal ion complexes were prepared and studied in acetonitrile solution showing good luminescence in the case of Nd3+, Yb3+, and Er3+ions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Methyl N‐Acetyl‐4‐amino‐2,4,6‐trideoxy‐3‐C‐methyl‐α‐L‐rhamnohexopyranoside − Towards Elucidation of the Relative Configuration of Saccharocarcin E Sugar
Authors: Langner Martin , Laschat Sabine , Grunenberg Jörg 
Published: March 2003

AbstractL‐Olivomycal 8, obtained from L‐rhamnose (10) in six steps, was used as a precursor for the preparation of methyl N‐acetyl‐4‐amino‐2,4,6‐trideoxy‐3‐C‐methyl‐α‐L‐rhamnohexopyranoside (5b). The amino group at C‐4 of 5b was introduced by intramolecular nucleophilic displacement of a (trichloromethyl)imidate derived from 8, yielding the 3,4‐trans‐(trichloromethyl)oxazoline 13 with retention of configuration. Compound 13 was further converted into the N‐acetamide 14 by basic hydrolysis and subsequent acetylation. N‐Iodosuccinimide‐promoted glycosylation and reductive dehalogenation yielded the target molecule 5b, together with its β epimer 5c (α/β = 85:15). Comparison of the NMR spectroscopic data of 5b with those of saccharocarcin E sugar and several other 4‐amino‐2‐deoxyhexoses revealed similarities between saccharocarcin E sugar and kijanimicin derivative 23, which suggest the proposed β‐L‐xylo‐hexopyranose configuration 4d for saccharocarcin E sugar. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
D‐Glucose as a Pentavalent Chiral Scaffold
Authors: Opatz Till , Kallus Christopher , Wunberg Tobias , Schmidt Wolfgang , Henke Stefan , Kunz Horst 
Published: March 2003

AbstractA novel carbohydrate‐based scaffold for combinatorial chemistry has been developed. This scaffold allows the selective attachment of five different side chains, giving rise to products of enormous structural diversity. As a demonstration of its usefulness, a series of model compounds has been prepared in high purity and yield by multistep parallel synthesis on a solid phase. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)