bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal transduction for interleukin‐3‐dependent leukotriene synthesis in normal human basophils: opposing role of tyrosine kinase and protein kinase C
Authors: Krieger Martin , Tscharner Vinzenz Von , Dahinden Clemens A. 
Published: March 2007

AbstractThe intracellular signaling pathways regulating the synthesis of leukotrienes by myeloid cells are largely unknown. In addition, the signal transduction mechanisms utilized by the cytokine receptor family are still poorly understood. The fact that in mature human basophils the synthesis of leukotriene C4 (LTC4) induced by C5a is strictly dependent on a short preincubation with the cytokine interleukin‐3 (IL‐3), allowed us to investigate the metabolic requirements for LTC4 synthesis, and also to provide some information on early signal transduction mechanisms of IL‐3 in these differentiated, non‐dividing blood leukocytes. IL‐3 itself does not alter intracellular free calcium concentration ([Ca2+]i) in basophils, whereas C5a induces a transient rise independent of IL‐3 pretreatment, indicating that the priming effect of IL‐3 cannot be explained by alterations in [Ca2+]i changes. The protein kinase C inhibitor staurosporine did not inhibit C5a‐induced histamine release nor IL‐3‐dependent LTC4 formation in contrast to the IgE receptor‐dependent basophil response. Activation of protein kinase C (PKC) by phorbol‐12‐myristate‐13‐acetate (PMA) induced histamine release without leukotriene formation. PMA‐treated basophils did not produce LTC4 in response to C5a. Rather, PMA blocked the IL‐3 effect on C5a‐induced LTC4 synthesis. Only the C5a signal but not the IL‐3 effect was pertussis toxin sensitive. Two unrelated tyrosine kinase inhibitors, tyrphostin RG‐50864 and herbimycin A, were both very efficient blockers of IL‐3‐dependent lipid mediator formation whereas C5a‐induced histamine release was preserved. Thus LTC4 formation does not require activation of a staurosporine‐sensitive serine/threonine kinase. To the contrary, IL‐3‐dependent LTC4 formation appears to be regulated by serine/threonine and tyrosine phosphorylation in an antagonistic manner.
Expression and role of interleukin‐2 receptor β chain on CD4−CD8+ T cell receptor αβ+ cells
Authors: Takeuchi Yumiko , Tanaka Toshiyuki , Hamamura Keisuke , Sugimoto Tsuneaki , Miyasaka Masayuki , Yagita Hideo , Okumura Ko 
Published: March 2007

AbstractUsing anti‐murine interleukin‐2 receptor β chain (IL‐2Rβ) monoclonal antibody (mAb), we have examined the expression of IL‐2Rβ on murine thymocyte subpopulations. We found that it was constitutively expressed on 1 %‐4% of thymocytes in an almost mutually exclusive fashion with IL‐2Rα. The expression of IL‐2Rβ is developmentally regulated. While it is expressed mainly on T cell receptor βδ+ (TcRγδ+) cells during fetal age, the major subpopulation expressing IL‐2Rβ in adult mouse shifts to CD4−CD8−TcR αβ+ thymocytes. A considerable portion of CD4−CD8− TcR αβ+ cells in other organs, including spleen, bone marrow and liver, was also found to express IL‐2Rβ. In fetal thymus organ culture, the above thymocyte subset was induced to expand in response to exogeneous IL‐2, and the expansion was inhibited by addition of anti‐IL‐2Rβ mAb, suggesting that IL‐2Rβ is functional in this subpopulation. However, in vivo blockade of the IL‐2/IL‐2R pathway with the mAb did not exert any effects on the appearance of CD4−CD8− TcR αβ+ cells both in the thymus and the periphery. This indicates that the development of CD4−CD8− TcR αβ+ cells is not solely controlled by IL‐2 but also by other complex elements.
CD59 molecule: A second ligand for CD2 in T cell adhesion
Authors: Deckert Marcel , Kubar Joanna , Zoccola Didier , Bernard‐Pomier Ghislaine , Angelisova Pavla , Horejsi Vaclav , Bernard Alain 
Published: March 2007

AbstractThe T cell surface molecule CD2 forms, with its counter‐receptor CD58 (LFA‐3), a powerful adhesion/activation pathway. There is some evidence that CD2 might bind more than a single ligand. Chinese hamster ovary cells (CHO) expressing human CD59 after cDNA transfection (CD59+CHO) form rosettes with human T cells; these rosettes are inhibited in a dose‐dependent fashion by the CD59 monoclonal antibody (mAb) H19 and by the CD2 mAb O275 known to block natural rosettes, but not by the CD2R mAb D66, a poor rosette blocker. CD2+CHO transfectants form rosettes with human erythrocytes; these rosettes are inhibited by the CD59 mAb H19 in addition to CD2 mAb O275 and CD58 mAb; murine thymoma cells expressing human CD2 form rosettes with CD59+CHO cells that again are blocked by CD59 H19 and by CD2 O275 mAb. In a marked contrast with H19, two others CD59 mAb, YTH 53.1 and MEM 43, which react with a different epitope on CD59, led to a 50% −70% increase of the number of cells forming rosettes. In addition to rosette experiments, the binding of 125I‐labeled CD59 molecules to CD2+CHO cells was specifically inhibited by unlabeled CD59 molecule and CD2 mAb. Furthermore, the binding of CD59 molecules to resting T cells induced expression of CD2R epitopes. These results directly show that CD2 binds CD59 and that subtle molecular changes occur upon binding.
Cloning and sequence analysis of two isotypic IgM heavy chain genes from Atlantic salmon, Salmo salar L
Authors: Hordvik Ivar , Voie Ann Mari , Glette Johan , Male Rune , Endresen Curt 
Published: March 2007

AbstractA leukocyte cDNA library from Atlantic salmon, based on oligo‐dT priming, was constructed in λ‐gt10. Immunoglobulin heavy chain (IgH) cDNA were isolated from the library using a specific probe generated by polymerase chain reaction (PCR) between two conserved areas within the variable region (second and fourth frame region). Two cDNA clones encoding the entire constant region of membrane‐bound IgH, and one cDNA encoding the entire constant region of secretory IgH were sequenced, revealing messages from two isotypic IgM genes. Both genes were shown to be present in haploid embryos and have been isolated from a genomic library, the exons and deduced amino acid sequences of which are presented here (salmon CHA and CHB). The splicing of transcripts encoding the membrane‐bound IgH excises the whole fourth exon as in other teleosts. The nucleotide and amino acid identity between salmon CHA and CHB are 98.2 %, and 96.2%, respectively. Two subfractions of IgM from Atlantic salmon separated by ion chromatography can be explained by a net exchange of basic residues in salmon CHB compared to CHA. The finding of two closely related salmon CH genes is in accordance with the quasi‐tetraploid state of the Atlantic salmon genome.
Altered major histocompatibility complex‐restricted antigen recognition by T cells from elderly humans
Authors: Schwab Risë , Russo Carlo , Weksler Marc E. 
Published: March 2007

AbstractPositive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)‐restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC‐restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen‐presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one‐half of the influenza‐specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80% of the MHC‐nonrestricted influenza‐specific T cell clones expressed the γ/δ T cell receptor, 20% of these clones expressed the α/β T cell receptor. Thus, changes in MHC‐restricted antigen recognition by T cells and in altered distribution of α/β versus the γ/δ T cell receptor bearing antigen‐specific T cell clones occur with aging.
α Heavy chain disease αmRNA contain nucleotide sequences of unknown origins
Authors: Fakhfakh Faïza , Dellagi Koussay , Ayadi Hammadi , Bouguerra Annie , Fourati Rashid , Ayed Farhat Ben , Brouet Jean Claude , Tsapis Andréas 
Published: March 2007

AbstractHuman α heavy chain disease is characterized by the production of abnormally short α IgH chains. In previously published cases it has been found that the malignant cells produce abnormal α mRNA, lacking VH and CH1 sequences and composed of a leader sequence peptide, sequences of variable length (69 to 84 bp) and of unknown origin, followed by normal CH2 and CH3 sequences. In this study we established the nucleotide sequence of α mRNA for six cases of α heavy chain disease. We observed that all six α mRNA lack the VH and CH1 sequences as do those previously described. They also contain in‐frame inserts of unknown origin between the leader peptide and the normal CH2 and CH3 coding sequences. These inserts are of variable length (42 to 105 bp) and they are unrelated. These results suggest the existence of a common mechanism defect leading to deletions/insertions in α heavy chain disease rather than a specific interaction between α1 IgH gene with a unique defined molecular species.
Role of T cell subsets during the recall of immunologic memory to Leishmania major
Authors: Müller Ingrid 
Published: March 2007

AbstractThe contributions of different T cell subpopulations to the maintenance of immunity during secondary Leishmania major infections were analyzed in healed, resistant animals by depletion of T cell subsets in vivo. The strong delayed‐type hypersensitivity mounted in immune genetically resistant mice upon challenge with viable promastigotes was mediated by both CD4+ and CD8+ T cells. Each T cell subpopulation alone contributes, although to a different extent, to the resolution of secondary lesions; both subsets, however, are required for an efficient and rapid healing of the secondary lesions and the decrease in the parasite burden in infected tissues.The results indicate that in immune, genetically resistant CBA mice, the activity of both T cell subsets is required for successful resistance to reinfection and an efficient maintenance of immunity.
Cryptic T cell epitopes in polymorphic immunoglobulin regions: Evidence for positive repertoire selection during fetal development
Authors: Chen Jian‐Jun , Kaveri Srinivas‐Venkatesh , Kohler Heinz 
Published: March 2007

AbstractThe adult T cell repertoire is the result of positive and negative intrathymic selective processes. Since non‐self antigens are not present in the thymus, self peptides are believed to play a role in the thymic T cell selection. T cell lines raised against a peptide from the second complementarity‐determining region (CDR2) of the S107 germ‐line immunoglobulin (Ig) do not respond to the intact Ig, indicating that in adult animals this CDR2 epitope is cryptic in the context of intact S107 Ig. To show that the response to self Ig peptide is the result of positive selection, the fetal expression of the S107 germ‐line Ig was suppressed by maternal anti‐idiotype (Id) injection. Id S107‐suppressed mice responded poorly to the CDR2 peptide, indicating that S107 Ig selects positively T cells responding to a polymorphic self epitope. Cross‐reactivity of cryptic self Ig with non‐self epitopes could be a mechanism to increase the T cell repertoire for foreign antigens.
Interferon‐α prevents endotoxin‐induced mortality in mice
Authors: Tzung Shie‐Pon , Mahl Thomas C. , Lance Peter , Andersen Valerie , Cohen Stefan A. 
Published: March 2007

AbstractEndotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram‐negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon‐α A/D (rIFN‐α) markedly inhibited this LPS‐elicited TNF production by Kupffer cells. The effects of rIFN‐α were further tested in C57BL/6 mice receiving a lethal dose (400 μg/mouse) of LPS. All LPS‐treated mice died within 2 days. Pretreatment with rIFN‐α 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN‐α was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post‐treatment with rIFN‐α. Subsequently, experiments were carried out to test the efficacy of delayed rIFN‐α treatment. A significant protective effect was still apparent when rIFN‐α was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN‐α might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production.
Functional role of α2/β1 and α4/β1 integrins in leukocyte intercellular adhesion induced through the common β1 subunit
Authors: Campanero Miguel R. , Arroyo Alicia G. , Pulido Rafael , Ursa Angeles , de Matías Milagros S. , Sánchez‐Mateos Paloma , Kassner Paul D. , Chan Bosco M. C. , Hemler Martin E. , Corbí Angel L. , de Landázuri Manuel O. , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractWhereas all of the integrins in the VLA protein subfamily are involved in cell‐extracellular matrix interactions, only VLA‐4 (through the α4 subunit) has been implicated in the triggering of intercellular adhesion. Here we describe that the VLA protein β1 subunit (CD29) is also involved in the induction of homotypic cell aggregation. We have obtained three novel anti‐β1 monoclonal antibodies (mAb) with the ability to induce cell aggregation on different leukocyte cell types. These mAb recognize an antigenic site on the common β1 chain of VLA proteins which is topographically and/or functionally distinct from other epitopes previously defined by several prototype anti‐β1 mAb. Induction of cell aggregation by anti‐β1 mAb is epitope specific, isotype and Fc independent, and displays kinetics similar to α4‐mediated aggregation. This cell aggregation requires an intact cellular metabolism, the presence of divalent cations in the extracellular medium, and the integrity of the cytoskeleton. We also have found that the Na+/H+ antiporter may be essential for this process. For Ramos cells, which bear only the VLA α4/β1 heterodimer, intercellular adhesion induced through the VLA‐β1 chain could be selectively inhibited by other anti‐β1 mAb as well as by anti‐α4 mAb. Interestingly, anti‐β1 mAb which induced strong aggregation of VLA‐α2‐ or VLA‐α4‐transfected K562 cells, had minimal effect on the α2− α4− α5+ K562 cell line. Furthermore, the β1‐mediated induction of cell aggregation on α2‐K562‐ and α4‐K562‐transfected cells was blocked by preincubation with either anti‐α2 or anti‐α4 mAb, respectively, as well as by other anti‐β1 mAb. Interestingly, parental K562 cells were able to interact with both α2‐ and α4‐transfected K562 cells, thus suggesting that counter‐receptors for both integrins (VLA‐2 and VLA‐4) might exist on these cells. Together these results provide strong evidence supporting the involvement of α2/β1 and α4/β1 heterodimers in intercellular interactions and underline the pivotal role of the common β1 chain of VLA proteins in the integrin‐mediated induction of cell aggregation.
Short peptides assist the folding of free class I heavy chains in solution
Authors: Elliott Tim , Cerundolo Vincenzo , Townsend Alain 
Published: March 2007

AbstractPrevious experiments have shown that short peptides coresponding to naturally processed epitopes of viral antigens can induce a conformational change in the class I heavy chain (HC) to which they bind in the fully assembled molecule. Here, we present evidence that the mechanism for this conformational change may involve binding of peptide to a partially unfolded form of free HC, followed by its subsequent folding. These results may be important for understanding the way in which class I molecules are assembled in vivo, and how certain epitopes are selected for presentation to T cells.
Binding of T cell receptor to major histocompatibility complex class II‐peptide complexes at the single‐cell level results in the induction of antigen unresponsiveness (anergy)
Authors: Celis Esteban , Saibara Toshiji 
Published: March 2007

AbstractUsing dispersion cultures performed in semi‐solid medium we demonstrate here that the interaction of T cell antigen receptor molecules with Ia‐peptide complexes on the same cell surface results in T cell activation, without the production of lymphokines. This recognition of antigen at the single‐cell level, induced a state of anergy which was not due to a decrease of surface T cell antigen receptor/CD3 complexes. The induction of anergy by peptide could not be prevented by the addition of various co‐stimulatory signals, including antibodies to CD28, or CD2, high doses of interleukin‐2 or phorbol ester.
Relative roles of decay‐accelerating factor, membrane cofactor protein, and CD59 in the protection of human endothelial cells against complement‐mediated lysis
Authors: Brooimans Ricardo A. , van Wieringen Patrick A. M. , van Es Leendert A. , Daha Mohamed R. 
Published: March 2007

AbstractHuman umbilical vein endothelial cells (HUVEC) were found by Western blot analysis to express three membrane‐bound C regulatory proteins, decay‐accelerating factor (DAF), membrane cofactor protein (MCP) and CD59. DAF was detected on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis as a 70‐kDa molecule under nonreducing conditions in 2% deoxycholate extracts of HUVEC, MCP as a 63‐kDa protein and CD59 as a 20‐kDa molecule. Northern blot analysis revealed the presence of two species of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for DAF, with sizes of about 2.0 kb and 2.7 kb. MCP mRNA was detected at 4.2 kb and a CD59 cDNA probe hybridized with three mRNA species with sizes of about 800, 1400 and 2000 bp. DAF and CD59 were released from the surface of HUVEC by phosphatidylinositol‐phospholipase C, demonstrating that both are attached to the cell membrane by means of a glycolipid anchor. The relative contribution of DAF, MCP and CD59 in regulating the sensitivity to lysis of HUVEC by autologous complement was determined by incubation of sensitized endothelial cells with F(ab′)2 fragments of polyclonal antibodies raised against these proteins. The susceptibility of sensitized cells to lysis by homologous complement was markedly increased in the presence of F(ab′)2 anti‐CD59 and to a lesser, but significant, extent in the presence of F(ab′)2 anti‐DAF. F(ab′)2 anti‐MCP did not significantly alter the susceptibility of HUVEC to complement‐mediated lysis.
Regulation of tumor necrosis factor (TNF)‐α synthesis and TNF receptors expression in T lymphocytes through the CD2 activation pathway
Authors: Santis Ana G. , Campanero Miguel R. , Alonso Jose L. , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractThe involvement of the CD2 (T11) molecule, an alternative activation pathway for T lymphocytes, in the regulation of tumor necrosis factor (TNF)‐α/TNF receptor system in human T lymphocytes has been investigated. It has been found that both TNF‐α synthesis and secretion were induced after incubation of purified T lymphocytes with the appropriate mitogenic combination of antibodies specific for two different epitopes on the CD2 molecule. Moreover, TNF‐α secretion was also observed by activation of T lymphocytes either through CD3 or CD69 molecular pathways, or with other stimulating agents such as Ca2+ ionophore in combination with phorbol esters. The expression of TNF receptors has been studied in both nonactivated and CD2‐activated T lymphocytes. Unstimulated T cells weakly expressed a functional 75‐kDa receptor form, whereas they lacked detectable levels of the 55‐kDa receptor form. Triggering of T cell activation through the CD2 molecule also markedly increased the expression of the p75‐kDa TNF receptor form, but did not exert any inductive effect on the expression of the p55‐kDa TNF receptor. In addition, we have found that TNF‐α enhanced the proliferative response triggered by the mixture of anti‐CD2 monoclonal antibodies. Taken together, these results support a role for the CD2 activation pathway in the functional regulation of TNF‐α/TNF receptor system in T lymphocytes, and reinforce the view of CD2 as an alternative pathway for regulation of the cytokine network that modulates the function of T lymphocytes.
Peritoneal sanctuary for human lymphopoiesis in SCID mice injected with human peripheral blood lymphocytes from Epstein‐Barr virus‐negative donors
Authors: Hoffmann‐Fezer Gertrud , Kranz Bernd , Gall Claudius , Thierfelder Stefan 
Published: March 2007

AbstractThe successful engraftment in SCID mice of intraperitoneally (i.p.) injected human lymphocytes (hu‐PBL‐SCID) and the failure of intravenously injected peripheral blood lymphocytes (PBL) directed the present study to investigate the early events of donor cell proliferation in the peritoneal cavity. We found focal lymphocyte engraftment together with histio‐monocytic interleukin (IL)‐6+ cell phenotypes which must have been transferred with the human cell inoculum, which could explain certain immune functions observed in hu‐PBL‐SCID chimeras. Following i.p. injection of 108 PBL, human cells suspended in peritoneal fluid as well as those adherent to the serosal peritoneum and abdominal organs were investigated by immunocytology and immunohistology. Human cells were found to form foci consisting predominantly of proliferating human lymphoblastoid CD3+ cells, which were mostly activated HLA‐DR+ CD8+ lymphocytes. Among the lymphoid cells larger epithelioid‐like cells were found to belong to the monocytic series and to stain strongly with anti‐HLA‐DR and anti‐CD11c antibodies. Some of these cells were also positive with anti‐ICAM and anti‐IL‐6. Congenic as well as allogeneic mouse PBL, injected i.p. into SCID mice, temporarily produced analogous foci, which shifted later on to foci similar in appearance to milky spots. However, the human cell foci appeared less compact, more closely resembling in vitro‐culture soft agar colonies. It is possible that cytokines in the human histio‐monocytic cells of the foci may have a feeder effect on the human lymphocytes and be a prerequisite for proliferation of human PBL in SCID mice. The observed early HLA‐DR activation of human lymphocytes in the peritoneal foci could reflect triggering of immune reactions like xenogeneic graft‐versus‐host reactions in the peritoneal site, where the human CD11c+ HLA‐DR+ histio‐monocytic cells may act as antigen‐presenting cells.