bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Th2‐biased lymphatic filarial patients, responses to purified protein derivative of Mycobacterium tuberculosis remain Th1
Authors: Sartono Erliyani , Kruize Yvonne C. M. , Kurniawan Agnes , Maizels Rick M. , Yazdanbakhsh Maria 
Published: March 2007

AbstractNatural infection with filarial nematode parasites results in immune responses skewed towards T helper (Th)2, while infection with mycobacteria shows many characteristics of a Th1‐dominated response. Cytokines typifying Th1, interferon (IFN)‐γ, and Th2, interleukin (IL)‐4, were measured following stimulation of peripheral blood mononuclear cells from filarial patients with Brugia malayi adult worm antigen (BmA) and purified protein derivative of Mycobacterium tuberculosis (PPD). In response to PPD, only 1 out of 81 patients produced IL‐4, and this at an amount (4.4 pg/ml) just above the detection limit, whereas 59% of patients responded to BmA by releasing IL‐4. Conversely, substantial quantities of IFN‐γ were released in response to PPD (geometric mean 37.43 U/ml) compared to low BmA‐stimulated IFN‐γ production in the same patients (geometric mean 5.02 U/ml). These results demonstrate that the strong skewing of the cytokine environment towards Th2 in filarial patients in vivo does not influence the predominance of a Th1 type immune response to PPD.
The differentiation of human memory B cells into specific antibody‐secreting cells is CD40 independent
Authors: Silvy Anne , Lagresle Chantal , Bella Chantal , Defrance Thierry 
Published: March 2007

AbstractIt is generally accepted that memory B cells can be defined by their ability to produce, upon antigenic challenge, somatically mutated antibody molecules characterized by an increased affinity and by the expression of a downstream heavy chain isotype. However, the inability to isolate this particular B cell compartment has precluded the study of memory B lymphocyte physiology in man. We previously reported on the identification of an IgD− B cell subset in human tonsils that we defined as CD38− B cells, whose phenotype is highly reminiscent of that of memory B lymphocytes from the splenic marginal zone of rodents. In the present study, we developed a model of the measles virus (MV)‐specific secondary antibody response in vitro to assess the presence of memory B lymphocytes in different B cell subsets isolated from human tonsils and explore the activation requirements of human memory B cells. Our findings show that the memory B cell pool resides in the CD38− B cell subpopulation and that the differentiation of MV‐activated memory B cells into antibody‐secreting cells can be achieved upon co‐stimulation with interleukin (IL)‐2 and IL‐10, but does not require engagement of CD40. Interestingly, the CD40‐mediated signal was found to synergize with Ig‐cross‐linking agents for the proliferation of memory B cells, but strongly suppressed their capacity to differentiate along the plasmacytoid pathway. Collectively, our results suggest that the CD40 signaling pathway is instrumental for the clonal expansion of the memory B cell pool, but does not operate in the later phase of the response, which allows their maturation into antibody‐secreting cells.
Expression of monocyte chemoattractant protein‐1 and interleukin‐8 receptors on subsets of T cells: correlation with transendothelial chemotactic potential
Authors: Qin Shixin , Larosa Greg , Campbell James J. , Smith‐Heath Heidi , Kassam Nasim , Shi Xiaojie , Zeng Ling , Butcher Eugene C. , MacKay Charles R. 
Published: March 2007

AbstractThe differential expression of chemokine receptors may be an important mechanism for the regulation of T cell migration. To test this, we examined the expression and function of the monocyte chemoattractant protein (MCP)‐1 and interleukin (IL)‐8 receptors on various populations of T cells. Using a simple and reliable transendothelial chemotaxis assay, both MCP‐1 and IL‐8 were shown to be chemotactic for subsets of blood T cells, although the relative response varied from donor to donor. To examine receptor expression and correlate it with chemotaxis of T cell subsets, monoclonal antibodies (mAb) to the receptors were produced by immunizing mice either with synthetic peptides (MCP‐1 receptor), or with receptor transfectants (IL‐8 receptors A and B). A flow cytometric analysis of blood T cells with an anti‐MCP‐1 receptor mAb revealed low expression on the CD26hi subset and undetectable expression on other T cells. Staining of T cells with anti‐IL‐8RA and anti‐IL‐8RB showed much higher levels of expression, but only on a subset of CD3+ cells which were CD8+ and CD56−. That IL‐8 and MCP‐1 attracted distinct subsets of T cells was best illustrated using the CD26 marker, since IL‐8R+ T cells were CD26−, whereas T cells expressing detectable MCP‐1R or which responded to MCP‐1 in chemotaxis assays were CD26hi. T cells activated in vitro with anti‐CD3 up‐regulated expression of the MCP‐1 receptor, but not the IL‐8 receptors, and were attracted to MCP‐1 much more efficiently than resting T cells. These results show that there is a clear distinction between the IL‐8‐ and MCP‐1‐responsive T cell populations and that chemokine receptor expression on T cells may be regulated with respect to lineage as well as cellular activation.
Natural killer clones recognize specific soluble HLA class I molecules
Authors: Carbone Ennio , Terrazzano Giuseppe , Colonna Marco , Tuosto Loretta , Piccolella Enza , Franksson Lars , Palazzolo Giovanni , Pérez‐Villar Juan José , Fontana Silvia , Kärre Klas , Zappacosta Serafino 
Published: March 2007

AbstractEnhancement of major histocompatibility complex (MHC) class I expression leads to protection from natural killer (NK) cell recognition in several systems. MHC class I gene products are released from the cell surface and can be found in sera as soluble forms. To investigate the possible immunoregulatory role of soluble HLA (sHLA) in NK cell‐target recognition, several sHLA antigens were studied for their ability to induce NK cell cytotoxicity modulation. NK cell‐target recognition was inhibited by the addition of sHLA during the cytotoxicity assay. Our results indicate that sHLA molecules can down‐regulate NK killing at the effector level. Moreover, different NK clones are able to specifically recognize different sHLA antigens. Kp43 molecules seem to be involved in the NK recognition of sHLA‐B7.
Effects of interferon‐α on cytokine profile, T cell receptor repertoire and peptide reactivity of human allergen‐specific T cells
Authors: Parronchi Paola , Mohapatra Subra , Sampognaro Salvatore , Giannarini Loretta , Wahn Ulrich , Chong Pele , Mohapatra Shyam , Maggi Enrico , Renz Harald , Romagnani Sergio 
Published: March 2007

AbstractA large panel of T cell clones (TCC) specific for the recombinant form of Poa pratensis allergen (rKBG7.2 or Poa p9) were established from the peripheral blood of a grass pollen‐sensitive donor in the absence or presence of recombinant interferon‐α (IFN‐α) in bulk culture and their pattern of cytokine secretion, peptide reactivity and TCR Vβ repertoire was examined. The majority of allergen‐specific TCC derived in absence of IFN‐α produced high amounts of interleukin‐4 (IL‐4) and IL‐5 but not IFN‐γ (Th2 cells), while most of TCC derived in presence of IFN‐α produced IFN‐γ but not, or limited amounts of, IL‐4 and IL‐5 (Th1 or Th0 cells). Of 24 TCC established in the presence of IFN‐α, 22 were able to recognize a single allergen peptide, p26, while none of the clones established in the absence of IFN‐α showed a similar specificity. The majority of both clones expressed the Vβ2 element regardless of whether they were established in the presence of IFN‐α, but the presence of IFN‐α favored the expansion of Vβ2+, Vβ17+ and Vβ22+ Poa p9‐specific T cells, whereas in the absence of IFN‐α, other TCR Vβ‐bearing T cells (Vβ5, Vβ6.7 and Vβ14) were expanded in addition to Vβ2+ T cells. None of Vβ2+ clones established in the absence of IFN‐α reacted with p26, whereas all the Vβ2+ clones established in its presence responded to this peptide. IFN‐α also shifted the TCR Vβ repertoire of both Poa p9‐ and Lolium perenne group 1 (Lol p1)‐specific T cell lines generated from the same patient and from a different grass‐sensitive individual. These data demonstrate that IFN‐α modulates the development of allergen‐specific T cells in vitro, and suggest that IFN‐α may represent an useful tool for novel immunotherapeutic approaches in allergic disorders.
Quantitative analysis of multiple V‐region interactions among normal human IgG
Authors: Ayouba Ahidjo , Peltre Gabriel , Coutinho Antonio 
Published: March 2007

AbstractThere is to date no quantitative method for scoring putative V‐region interactions among serum antibodies, and the available qualitative techniques are not amenable to routine utilization. This deficit may explain the paucity of observations on the characteristics of the immune network, in contrast with the multiplicity of phenomenological descriptions on idiotype regulation.We describe here a novel methodology that uses isoelectric focusing (IEF) to resolve human F(ab′)2 preparations from large pools of normal serum IgG into multiple bands, and computer‐aided data processing to analyze interactions between the resulting blotted proteins and normal serum IgG from individual donors. Our results show that in all normal human sera tested, there are IgG‐mediated interactions with a large number of IEF fractions of human F(ab′)2. These interactions are V region specific, as assessed by inhibition experiments and by the lack of binding of IgG monoclonal antibodies, and are characterized by average affinities that are in the micromolar range, as measured by surface plasmon resonance.
Epidermal growth factor can replace thymic mesenchyme in induction of embryonic thymus morphogenesis in vitro
Authors: Shinohara Takashi , Honjo Tasuku 
Published: March 2007

AbstractThe thymus is surrounded by a thin layer of mesenchyme and the epithelial‐mesenchymal interaction is known to be essential for the thymus development. To clarify the roles of mesenchyme in the thymus lobule formation that occurs around embryonic days 14–15 in vivo, we set up a three‐dimensional organ culture system. The epithelium of embryonic day 13 thymic primordium was separated from the mesenchyme and cultured in Matrigel (reconstituted basement membrane). Addition of the mesenchyme to a chamber separated by a membrane filter induced the lobule formation of the thymic epithelium in vitro. We found that epidermal growth factor (EGF) can replace the mesenchyme for lobulation of the embryonic thymus in vitro. Among other growth factors tested, only transforming growth factor (TGF)‐α was as effective as EGF, in agreement with the fact that EGF and TGF‐α bind to the same receptor. These results suggest that EGF or its family members may be involved in morphogenesis and differentiation of the thymus gland epithelium, although we cannot exclude the possibility that other unknown factors are required in vivo.
One cause for the apparent inability of human T cell clones to function as professional superantigen‐presenting cells is autoactivation
Authors: Nisini Roberto , Fattorossi Andrea , Ferlini Cristiano , D'Amelio Raffaele 
Published: March 2007

AbstractHuman T cell clones (TCC) are antigen‐presenting cells (APC) able to present peptides and superantigens (SAg) and to process and present intact proteins. TCC express major histocompatibility complex (MHC) class II antigens and molecules involved in the accessory signal delivery, such as B7.1 and B7.2/B70. Notwithstanding these observations, the role of professional APC has been often denied to T cells because anergy of responder T cells rather than proliferation has been observed following the TCC presentation in the absence of added professional APC. Here, we show that upon stimulation with free SAg, TCC undergo proliferative responses followed, after a 1‐week culture, by an SAg‐dependent unresponsiveness to T cell receptor (TCR)‐mediated stimuli, but not to interleukin‐2. The anergy induced by the SAg can not be prevented by the addition of autologous Epstein‐Barr virus (EBV)‐transformed B cells, indicating that the induction of anergy occurs also in the presence of conventional APC. Conversely, if the TCC are stimulated by SAg‐prepulsed irradiated APC, either EBV and TCC, the induction of anergy is not observed. After a 1‐week culture, in fact, TCC stimulated with APC‐bound SAg responded to TCR‐mediated stimuli, irrespective of the APC (EBV or TCC) used for the SAg presentation. Stimulation of TCC with free SAg in a semisolid medium that prevents T‐T cell contacts resulted in an activation followed by a state of anergy, suggesting that anergy is the consequence of SAg recognition at the single T cell level. These data indicate that the anergy observed in TCC upon a 1‐week culture in the presence of soluble SAg is not the result of an inherent inability of TCC to act as professional APC. Rather the phenomenon depends on the presence of soluble SAg, leading to T cell autostimulation.
T cell receptor‐γδ‐expressing fetal mouse thymocytes are generated without T cell receptor Vβ selection
Authors: Mertsching Elisabeth , Ceredig Rhodri 
Published: March 2007

AbstractWe investigated whether fetal mouse T cell receptor (TCR) γδ cells have been subjected to so‐called TCRβ selection at the CD25 stage of thymus development. To this end, we carried out a comparative three‐color flow microfluorimetric analysis of TCRβδ cells developing in the fetal, neonatal and adult thymus using monoclonal antibodies to CD2, CD8, CD24, CD25 and CD44. Day‐15 fetal TCRγδ cells were CD2+, suggesting an origin at a post‐CD25 stage. Molecular analysis of TCRβ rearrangements were also carried out. Thus, by semi‐quantitative polymerase chain reaction (PCR) amplification of Vβ6 and Vβ8 to Jβ2 rearrangements day‐15 fetal TCRγδ showed extensive TCRβ rearrangements, a finding confirmed by PCR amplification from single micromanipulated cells. Finally, sequencing analysis of 104 PCR‐amplified TCR VDJβ2 fragments showed that the majority (58%) were rearranged out of frame. Taken together, these phenotypic and molecular analyses suggest that fetal TCRγδ cells have not been subject to TCRβ selection.
CD31‐triggered rearrangement of the actin cytoskeleton in human natural killer cells
Authors: Poggi Alessandro , Panzeri Maria Carla , Moretta Lorenzo , Zocchi Maria Raffaella 
Published: March 2007

AbstractIn this report, we analyze whether CD31, also known as platelet‐endothelial cell adhesion molecule‐1 (PECAM‐1), can transduce an outside‐in signal in human natural killer (NK) lymphocytes in vitro. We show that CD31, but not HLA class‐I cross‐linking triggers an outside‐in transmembrane signal in NK lymphocytes, mediating cell spreading and cytoskeletal rearrangement. These phenomena are Mg2+, but not Ca2+ dependent, suggesting that signal transduction elicited by CD31 cross‐linking may involve an associated integrin. Two possible candidates would be αv and αL, whose function is known to depend on Mg2+. However, the CD31‐induced cytoskeletal rearrangement was not reduced by the use of αv‐ or αL‐specific F(ab′)2, suggesting that CD31 could transduce a signal by itself or by association with a still‐undefined integrin. Moreover, talin, but not vinculin or tubulin, appears to co‐localize with actin microfilaments in the membrane ruffles of NK cells that undergo cytoskeleton rearrangement following CD31 cross‐linking. Both spreading and cytoskeletal rearrangement appear to be regulated by intracellular cyclic‐3′,5′‐adenosine monophosphate (cAMP). Indeed, the activator of the adenylyl cyclase, forskolin, inhibited cell spreading and cytoskeletal rearrangement induced by CD31 cross‐linking. This phenomenon was also observed using the membrane‐permeants cAMP analog Sp adenosine‐3′,5′‐cyclic monophosphothioate (Sp‐cAMPS), but not its inactive isomer Rp‐cAMPS. Likewise, adhesion of NK lymphocytes to NIH/3T3 murine fibroblasts transfected with the cDNA encoding human CD31 was blocked by increasing intracellular cAMP levels. We suggest that intracellular cAMP may be involved in CD31‐mediated signal transduction, and may regulate NK‐endothelial cell adhesion and possibly, the tissue localization of NK cells.
Translatable immunoglobulin germ‐line transcript
Authors: Bachl Jürgen , Turck Christoph W. , Wabl Matthias 
Published: March 2007

AbstractDuring B cell differentiation, the functional genes encoding immunoglobulin (Ig) heavy (H) and light (L) chains are generated by two rearrangement processes ‐ VDJ rearrangement generates the exon encoding the Ig variable (V) regions, and the class switch reconstructs a rearranged Ig H gene by exchanging the segment encoding the constant (C) region, which determines the Ig class. Both types of rearrangement are preceded by transcripts originating from a transcriptional start site 5′ of the I exon, which is then spliced to the C exons. These germ‐line transcripts, which are thought to be necessary for the initiation of both types of rearrangement, are said to be sterile. We demonstrate here that the μ germ‐line transcript is translatable into a polypeptide chain, to which we assign the symbol ψ. Thus, protein products of these transcripts might be part of or signal to the recombinases that catalyze Ig gene rearrangement.
JNK, but not MAPK, activation is associated with Fas‐mediated apoptosis in human T cells
Authors: Wilson David J. , Fortner Karen A. , Lynch David H. , Mattingly Raymond R. , Macara Ian G. , Posada James A. , Budd Ralph C. 
Published: March 2007

AbstractFas is a cell surface molecule that is expressed on a wide array of cell types and triggers apoptosis. While in most situations Fas ligation activates programmed cell death, on resting T lymphocytes it can co‐stimulate proliferation with the T cell receptor (TCR)/CD3 complex. This incongruity suggests that Fas may elicit signaling events that overlap with those used by proliferation cues. We observe that in the human T cell line Jurkat and in human peripheral blood lymphocytes, Fas stimulation does not signal by the Ras/Raf‐1/mitogen‐activated protein kinase (MAPK) pathway or by increased intracellular calcium. Rather, Fas ligation strongly activates Jun kinase (JNK). This activity, as well as Fas‐induced apoptosis, is blocked by increased levels of cAMP. The balance between proliferation and apoptosis by Fas triggering of T lymphocytes may therefore reflect a signaling ratio between TCR activation of the Ras/Raf‐1/MAPK pathway versus JNK activation by Fas.
Soluble CD40 ligand induces expression of CD25 and CD23 in resting human tonsillar B lymphocytes
Authors: Burlinson Ellen L. , Graber Pierre , Bonnefoy Jean‐Yves , Ozanne Bradford W. , Cushley William 
Published: March 2007

AbstractIn this report, we describe the dose‐dependent increase in both CD25 and CD23 levels on resting human B cells in response to CD40 ligation, as mediated by soluble CD40 ligand (sCD40L) or anti‐CD40 antibody. In combination with interleukin (IL)‐4, sCD40L had limited additive effects on CD25 expression, but significantly enhanced CD23 expression on tonsillar B cells. Interferon‐γ (IFN‐γ) exerted no inhibitory effect upon increases in CD25 or CD23 driven by CD40 ligation with sCD40L or anti‐CD40 antibody. These data suggest that the induction of CD25 and CD23 genes by IL‐4 is mediated, at least in part, by an IFN‐γ‐sensitive component, whereas gene activation driven via CD40 ligation involves signaling pathways which are not sensitive to IFN‐γ.
Inhibition of interleukin‐6 synthesis in an animal model of septic shock by anti‐C5a monoclonal antibodies
Authors: Höpken Uta , Mohr Michael , Strüber Andreas , Montz Hildegard , Burchardi Hilmar , Götze Otto , Oppermann Martin 
Published: March 2007

AbstractThe complement activation fragment C5a was recently shown to induce interleukin (IL)‐6 synthesis by peripheral blood mononuclear cells. To understand better the role of C5a in cytokine regulation in vivo, we investigated the effects of complement depletion by cobra venom factor (CVF) or of anti‐C5a monoclonal antibodies (mAb) on IL‐6 generation in an animal model of septic shock. Complement‐depleted pigs which were subsequently challenged with Escherichia coli generated significantly (p < 0.05) less IL‐6 during the 6‐h observation period than complement‐sufficient controls. To address specifically the role of C5a in IL‐6 regulation, we produced a C5a(57–74) peptide‐specific mAb (T13/9) which neutralizes the bioactivity of porcine C5a. The mAb T13/9 does not crossreact with the precursor protein C5. The pretreatment of pigs with anti‐C5a mAb T13/9 prior to the induction of sepsis resulted in a decrease of over 75 % in serum IL‐6 bioactivity compared to control animals (p < 0.0001). These results indicate a role for C5a in the modulation of IL‐6 synthesis in Gram‐negative bacteremia.
Characterization of an epitope of the human cytomegalovirus protein IE1 recognized by a CD4+ T cell clone
Authors: Gautier Nicolas , Chavant Emmanuelle , Prieur Eric , Monsarrat Bernard , Mazarguil Honoré , Davrinche Christian , Gairin Jean Edouard , Davignon Jean‐Luc 
Published: March 2007

AbstractCD4+ T cells specific for human cytomegalovirus (HCMV) IE1 protein are potential effectors of the control of HCMV infection through cytokine production. Better knowledge of major histocompatibility complex (MHC)‐peptide‐T cell receptor (TcR) interactions in the CD4+ T cell response should result in a better design of immunizing peptides and is a prerequisite for the development of vaccines or anti‐cytomegalovirus therapy. In this study, the recombinant protein comprising residues 86–491 encoded by exon 4 of IE1 (GST‐e4) was cleaved by enzymatic digestion and analyzed by high pressure liquid chromatographymass spectroscopy (HPLC‐MS). We identified the 14‐residue epitope 162‐DKREMWMACIKELH‐175 recognized by an HLA‐DR8‐restricted clone, BeA3. Synthetic elongated, truncated and di‐Ala‐substituted peptides of the 18‐mer IE1 158‐IVPEDKREMWMACIKELH‐175 sequene were used to analyze the amino acid motifs involved in binding to HLA‐DR8 and recognition by the BeA3 clone. Substitutions which abolished (MW → AA), or decreased (RE → AA and MA → AA) T cell clone proliferation, cytokine production and cytotoxicity were identified. Loss of T cell function induced by the MW → AA substitution was associated with poor HLA‐DR8 binding. Decreased T cell function (RE → AA and MA → AA) was associated with good HLA‐DR8 binding, which suggested that these motifs were involved in TcR binding. Other substitutions induced potentiation of the T cell clone response: the IV → AA substitution induced stronger proliferation, but equivalent cytokine production, when compared with the reference peptide IE1 (158–175). CI → AA substitution induced strong potentiation of HLA‐DR8 binding, proliferation and interferon‐γ and interleukin‐4 production, possibly due to the removal of negative effects of Cys, Ile, or both side chains. Cytotoxicity was not improved by any substitution. Our results show modulation of the CD4+ T cell response according to the peptide residues involved in the HLA‐DR8‐peptide‐TcR interaction.