bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosolic targeting of hen egg lysozyme gives rise to a short‐lived protein presented by class I but not class II major histocompatibility complex molecules
Authors: Calin‐Laurens Veronique , Forquet Frédérique , Gerlier Denis , Rabourdin‐Combe Chantal , Mottez Estelle , Kanellopoulos Jean , Godeau François , Kourilsky Philippe 
Published: March 2007

AbstractA way to study the role of intracellular trafficking of an antigen in its presentation to T cells is to target the antigen to various cell compartments of the antigen‐presenting cells (APC) and compare the nature of the complexes associating major histocompatibility complex (MHC) molecules and antigenic peptides, expressed on the cell surface. MHC class I+ and MHC class II+ mouse L fibroblasts secreting hen egg lysozyme (HELs cells) or expressing HEL in their cytosol (HELc cells) were obtained after transfection with HEL cDNA and signal sequence‐deleted HEL cDNA, respectively. HEL was evidenced in both HELs‐and HELc‐transfected cells and the former type of transfectant secreted a large amount of HEL. However, HEL produced in the cytosol exhibited a short half‐life of less than 5 min. HEL‐derived peptides could not be shown biochemically either in HELc‐ nor in HELs‐transfected cells. We then studied the capacity of these cells to present HEL to HEL‐specific class I‐ and class II‐restricted T cells. Both cell types could be recognized by the HEL‐specific MHC class I‐restricted CTL clones. In contrast, MHC class II‐HEL peptide complexes, recognized by HEL‐specific helper T cell hybridomas, could be detected on MHC class II+ HELs‐ but not HELc‐transfected cells. In vivo experiments showed, however, that HELc‐transfected cells could provide host APC with HELc‐derived peptides able to associate with MHC class II molecules. This was inferred from the capacity of MHC class II− HELc‐transfected cells, unable by themselves to elicit any anti‐HEL antibody response, to prime syngeneic and allogeneic mice against HEL. The priming was revealed by the induction of an antibody response after a boost with an amount of HEL unable itself to elicit an antibody response.
Human complement factor H: two factor H proteins are derived from alternatively spliced transcripts
Authors: Estaller Cornelia , Weiss Elisabeth H. , Schwaeble Wilhelm , Dierich Manfred 
Published: March 2007

AbstractThe human complement factor H is an important component in the control of the alternative pathway of complement activation. We have previously shown that at least three factor H homologous mRNA species of 4.3 kb, 1.8 kb and 1.4 kb in length are constitutively expressed in human liver. In addition, several factor H‐related proteins have been detected in human sera using antibodies directed against the classical human factor H glycoprotein of 150 kDa. The structure of the additional polypeptides has not been shown so far. Circumstantial evidence suggests that the 1.8‐kb mRNA might encode the 43‐kDa factor H‐like polypeptide. Here we report the isolation, characterization and eukaryotic expression of the first full‐length cDNA representing the major 4.3‐kb mRNA and the 1.8‐kb mRNA of human factor H. We show that the 4.3‐kb transcript encodes the 150‐kDa‐factor H glycoprotein and the 1.8‐kb mRNA the 43‐kDa factor H polypeptide. The identity of the two cDNA in a region of 1400 nucleotides suggests that the two factor H‐related transcripts are derived from one gene by a process of alternative splicing.
A transcriptional enhancer of the mouse T cell receptor δ gene locus
Authors: Gill Laura Lee , Karjalainen Klaus , Zaninetta Daniela 
Published: March 2007

AbstractT cells express receptors for antigen on their surface (TcR) which consist either of α/β or of γ/δ polypeptide chains. Since the TcR δ chain gene is located within the TcR α chain gene locus, strict regulation of expression of the region must operate to ensure that the two loci are not concomitantly expressed in T cells bearing either α/β or γ/δ TcR. In this report it is demonstrated that elements within the mouse TcR δ gene locus, located between the Jδ2 and Cδ exons, enhance transcription from a heterologous promoter five‐ to tenfold in a T cell hybridoma expressing a TcR γ/δ, whereas enhancement was only twofold in an α/β‐bearing T cell hybridoma. No enhancement of expression was observed in a B cell hybridoma. The sequences responsible for this enhancing activity are largely confined to a 766‐bp Hae III DNA restriction fragment. A region within this DNA segment shows significant homology (73% identify) to a recently identified enhancer of the human TcR δ gene locus.
Evidence for a restricted idiotypic and epitopic specificity of anti‐thyroglobulin autoantibodies in patients with autoimmune thyroiditis
Authors: Dietrich Gilles , Kazatchkine Michel D. , Piechaczyk Martine , Pau Bernard 
Published: March 2007

AbstractAnti‐thyroglobulin (TG) autoantibodies from patients with autoimmune thyroiditis express a cross‐reactive α idiotype (Id) termed T44 which is not expressed by IgG from normal individuals. The present study demonstrates that the expression of the T44 Id is strongly associated with the recognition by anti‐TG autoantibodies of a specific epitopic cluster on human TG. The epitopic reactivity of anti‐TG autoantibodies was determined using a competitive inhibition assay with a panel of 15 monoclonal antibodies that define six antigenic clusters on TG. All T44+ autoantibodies from patients recognized cluster II, whereas no anti‐TG IgG from healthy individuals reacted with this region. Affinity columns of Sepharose‐bound intravenous therapeutic immunoglobulins which contain anti‐T44 activity, retained both T44 Id‐expressing antibodies and a subset of region II‐specific anti‐TG autoantibodies from patients with Hashimoto's disease. Restricted idiotypic and epitopic specificity may demarcate disease‐associated from natural anti‐TG autoantibodies, suggesting that qualitative rather than quantitative criteria should be used to identify pathological autoantibodies.
Biased expression of individual T cell receptor V gene segments in CD4+ and CD8+ human peripheral blood T lymphocytes
Authors: Grunewald Johan , Janson Carl Harald , Wigzell Hans 
Published: March 2007

AbstractThe expression of seven different α and β gene segments of the T cell receptor on normal human CD4+ and CD8+ T lymphocytes, respectively, was examined using V gene‐specific monoclonal antibodies. We found a statistically significant (p < 0.001) bias of the expression of four V gene products towards the CD4+ subpopulation. In every individual analyzed, the Vβ5.1 gene segment was expressed to a higher degree among CD4+ compared to CD8+ cells, with a median value of 4.8% among CD4+ cells and 1.5% among CD8+ cells. There was also a statistically significant skewness in the usage of the Vβ6.7, Vβ8 and Vβ12 gene segments towards the CD4+ T cell population, but not as dominating as for the Vβ5.1. Lymphocytes from umbilical cord blood showed similar skewed reactivities for the Vβ5.1, Vβ6.7 and Vβ12‐specific monoclonal antibodies. Aspects of positive and negative selection, as possible explanations for these findings, are discussed.
Expression of lineage‐restricted protein tyrosine kinase genes in human natural killer cells
Authors: Biondi Andrea , Rossi Vincenzo , Benvestito Serena , Paganin Carla , Allavena Paola , Mantovani Alberto , Perlmutter Roger M. 
Published: March 2007

AbstractThe hematopoietic lineage derivation, recognition structures and associated signal transduction pathways of CD3− natural killer (NK) cells have not been identified. Protein tyrosine kinases (PTK) structurally related to the product of the c‐src protooncogene are differentially expressed in distinct hematopoietic differentiation lineages and may participate in specific signal transduction pathways.The present study was aimed at characterizing the expression of src‐related PTK genes in normal human NK cells and in cells from patients with CD3− granular lymphocyte proliferative disease. CD3− normal NK cells had high levels of transcripts of the lck gene, which is highly expressed in T cells. CD8+ and CD8− NK cells expressed similarly high levels of Ick mRNA.In contrast, NK cells expressed very low levels (25‐80 times less than monocytes) of mRNA encoding the myelomonocytic PTK hck.NK cells also expressed fyn transcripts (p59fyn reportedly associates with the T cell receptor in T cells) and fgr transcripts, the latter observation confirming a previous report. The pattern of expression of the lineage‐restricted PTKs lck and hck in NK cells is consistent with the hypothesis of an ontogenic relationship of this population with the lymphocytic rather than myelocytic differentiation pathway. PTK expressed in NK cells may participate in signal transduction pathways in this cell population.
Dominant expression of the T cell receptor BALB invariant δ (BID) chain in resident pulmonary lymphocytes is due to selection
Authors: Sim Gek‐Kee , Augustin Andrei 
Published: March 2007

AbstractDuring ontogeny, the T cell receptor BALB invariant δ (BID) chain (Sim, G.‐K. and Augustin, A., Cell 1990. 61: 397) is generated in C57BL/6 fetal thymocytes at levels similar to those detected in BALB/c mice. Hence, the dominance of BID observed among resident pulmonary lymphocytes of BALB/c and of (BALB/c x C57BL/6) F1 and its absence in C57BL/6 mice is due to positive selection and peripheral expansion rather than to the inability of C57BL/6 mice to generate this particular rearrangement.
Anti‐HLA antigen class I heavy chain monoclonal antibodies inhibit human immunodeficiency virus production by peripheral blood mononuclear cells
Authors: Corbeau Pierre , Olive Daniel , Devaux Christian 
Published: March 2007

AbstractWe have examined the capacity of monoclonal antibodies (mAb) specific for HLA class I heavy chain to interfere with the human immunodeficiency virus (HIV) replicative cycle in human T cells. Among six anti‐HLA class I heavy chain‐specific mAb assayed, two mAb, RL4‐24‐6 and W6/32, were able to delay HIV1 and HIV2 cytopathic effect on MT4 cells, a human T cell leukemia virus type I (HTLVI) immortalized T cell line. mAb RL4‐24‐6, chosen for further studies, also inhibited HIV1 production by peripheral blood mononuclear cells (PBMC), and this inhibition was dose dependent. However, no effect was observed when mAb treatment was performed with either the CEM or Jurkat T cell lines. Our investigation of how RL4‐24‐6 interferes with the HIV replicative cycle revealed that: (a) incubation of PBMC with RL4‐24‐6 prior to HIV exposure did not change the susceptibility of these cells to HIV infection, (b) syncytia formation between CD4+ MT4 cells and HIV chronically infected PBMC was not affected by RL4‐24‐6 and (c) treatment of freshly infected PBMC with RL4‐24‐6, however, inhibited viral production. These data, together with those we previously reported using anti‐β2‐microglobulin (β2m) mAb, suggest that anti‐HLA class I/β2m complex mAb can modify an early step of the HIV replicative cycle without affecting the viral entry.
The presence of eosinophil‐activating mediators in sera from individuals with Schistosoma mansoni infections
Authors: Mazza Graziella , Thorne Kareen J. I. , Richardson Brian A. , Butterworth Anthony E. 
Published: March 2007

AbstractIgG antibodies and eosinophils kill schistosomula of Schistosoma mansoni in vitro, and there is now evidence to suggest that the main factor that contributes to the expression of purified IgG effector function is the degree of activation of the donor's eosinophils. This study was designed to identify serum‐derived activating factors in sera from individuals infected with S. mansoni. Such activating factors may be responsible for enhancing eosinophil cytotoxicity against schistosomula. Serum‐borne mediators were prepared by fractionation of sera from infected individuals by gel filtration high‐performance liquid chromatography. The eosinophil‐stimulating activity of these mediators was assayed by a new method which depends on the increased expression of the CR3 α chain (CD11b) on the surface of activated eosinophils. Sera from infected individuals exhibited different levels of eosinophil activation, and activation appeared to be due to several serum factors, including interleukin 5. In conclusion, our results suggest that eosinophil‐activating factors present in infection sera may not only be responsible for enhancing eosinophil cytotoxicity but also be necessary for its expression.
Major histocompatibility complex class II hyperexpression on B cells in interleukin 4‐transgenic mice does not lead to B cell proliferation and hypergammaglobulinemia
Authors: Müller Werner , Kühn Ralf , Rajewsky Klaus 
Published: March 2007

AbstractThe murine interleukin 4 (IL 4)‐encoding cDNA expressed under the control of the immunoglobulin heavy chain enhancer/promoter was inserted into the mouse germ line. All B cells present in the IL 4 transgenic mice show a marked increase in expression of class II histocompatibility (Ia) antigens compared to B cells from control mice. In vivo 5‐bromo‐2′‐deoxyuridine incorporation and cell cycle analysis revealed no significant increase in B cell proliferation in spleens of IL 4 transgenic mice compared to littermate controls. Likewise, serum immunoglobulin concentrations in IL4 transgenic mice were not increased. From these experiments we conclude that Ia hyperexpression on B cells per se does not induce activation of autoreactive T cells leading to B cell proliferation or hypergammaglobulinemia.
A role for adhesion molecules in contact‐dependent T help for B cells
Authors: Owens Trevor 
Published: March 2007

AbstractThe role of cell contact in T‐dependent B cell activation was examined. Small resting B cells from C57BL/6 mice were cultured with CBA‐derived, non‐alloreactive cloned T helper cells in anti‐T cell receptor Vβ8‐coated microwells. This induced polyclonal B cell activation to enter cell cycle (as measured by thymidine incorporation at 2 days) and to secrete immunoglobulin (as measured by an enzyme‐linked immunoassay detecting high‐rate Ig secretion at 5 days). The inclusion of monoclonal antibodies against LFA‐1, ICAM‐1 and CD4 in these cultures strongly inhibited antibody responses, although proliferative responses were only inhibited to about 50%. Inhibitory monoclonal antibodies did not significantly affect lipopolysaccharide‐induced responses, T cell activation to interleukin (IL) 3 secretion, nor did they inhibit the formation of multicellular clusters containing T and B cells. There was no correlation between the level of expression of adhesion molecules by T cells and their ability to induce B cell responses. Anti‐LFA‐1 abrogated T‐dependent responses to IL 2 which were inducible after 2 days in culture, but did not inhibit the induction of this IL 2 responsiveness. These results suggest that continued cell contact involving adhesion/accessory molecules induces B cells to proliferate and to respond to T cell lymphokines. A signaling role for cell interaction molecules on B cells is proposed, similar to the role of these and analogous molecules on T cells.
Expression of mouse IgA by transgenic mice, pigs and sheep
Authors: Lo David , Pursel Vernon , Linton Phyllis J. , Sandgren Eric , Behringer Richard , Rexroad Caird , Palmiter Richard D. , Brinster Ralph L. 
Published: March 2007

AbstractThe development of transgenic animal technology allows the introduction of desired traits into the germ line of mice and other animals. Since the production of antibody to various polysaccharide antigens can be protective against pathogenic bacteria, we generated transgenic mice, sheep and pigs carrying genes encoding the mouse α and χ chains for antibodies against phosphorylcholine (PC) to determine whether transgene antibody might be used to influence susceptibility to disease. High serum levels of mouse IgA were detected in transgenic mice and pigs but not in transgenic sheep. It has been noted that transgene immunoglobulin expression can suppress endogenous immunoglobulin gene rearrangement and expression, and indeed, in one mouse line, expression of the transgene resulted in < 10% of spleen B cells expressing endogenous IgM. Despite this suppression, significant levels of endogenous IgM were still secreted into the serum. Suppression of endogenous IgM expression was not seen in other mouse lines, nor was it seen in transgenic pigs. In the transgenic pigs, the mouse IgA was detected in the serum despite the absence of an intact mouse χ transgene, so the secreted antibody presumably included pig light chains. Little if any of the mouse IgA in these sera showed binding specificity for PC. In one of the founder sheep, mouse IgA was detectable in peripheral lymphocytes but not in serum. Mouse χ expression was not detected in the transgenic sheep harboring an intact χ transgene. These results illustrate the potential of introducing beneficial traits such as germ‐line‐encoded immunity into large mammalian species.
The role of oil and agalactosyl IgG in the induction of arthritis in rodent models
Authors: Rook Graham , Thompson Steve , Buckley Marion , Elson Chris , Brealey Richard , Lambert Claude , White Tony , Rademacher Thomas 
Published: March 2007

AbstractThe proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65‐kDa heat‐shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 μg of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day —10, or with 500 rad irradiation on day ‐ 2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50–75 days, although levels at 150–200 days were not affected.The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p < 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal (O) is raised, is more likely to evoke disease.Since oil granulomata are known to secrete interleukin 6, which has B cell‐regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6‐transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.
Induction of interleukin 2 (IL2) and interferon‐γ and enhancement of IL2 receptor expression by a CD26 monoclonal antibody
Authors: Plana Montserrat , Viñas Odette , de la Calle‐Martin Oscar , Lozano Francisco , Inglés‐Esteve Julia , Romero Matilde , Alberola‐Ila José , Yagüe Jordi , Vilella Ramön , Vives Jordi 
Published: March 2007

AbstractThe ability of the 134‐2C2 monoclonal antibody (mAb; CD26) to transmit an activation signal and to affect T cell proliferation has been studied. The 134‐2C2 mAb, although not being mitogenic by itself, is able to increase the proliferation of purified T cells in the presence of exogenous interleukin 2 (IL2) or phorbol 12‐myristate 13‐acetate (PMA). No effect of our mAb was observed on the proliferation of T cells induced by other stimuli such as Sepharose‐bound CD3 mAb, phytohemagglutinin or calcium ionophore. Since the co‐stimulatory effect of 134‐2C2 mAb on PMA‐induced T cell proliferation was strongly inhibited by an anti‐Tac antibody, its involvement on the IL2/IL2 receptor pathway was investigated. An increased IL2 secretion in T cells cultured with PMA plus 134‐2C2 mAb was observed and Northern blot analysis showed that the mAb 134‐2C2 acts synergistically with PMA favoring the induction of both IL2 and interferon‐γ mRNA synthesis, as well as the enhancement of IL2 receptor and transferrin receptor mRNA expression. Studies on mechanisms implicated in signal transduction showed that 134‐2C2 mAb modifies neither intracellular calcium levels nor phosphoinositide breakdown. Additionally, no effect was exerted on protein kinase C translocation. These data suggest that the CD26 antigen is involved in T cell activation in an IL2/IL2 receptor‐dependent pathway.
Surface expression by mononuclear phagocytes of an epitope shared with mycobacterial heat shock protein 60
Authors: Wand‐Württenberger Angela , Schoel Bernd , Ivanyi Juraj , Kaufmann Stefan H. E. 
Published: March 2007

AbstractBone marrow‐derived macrophages were stained with a variety of monoclonal antibodies (mAb) with specificity for the mycobacterial heat shock protein (hsp) 60 or with specific rabbit antiserum raised against mycobacterial hsp 60. The mAb ML30 as well as the specific antiserum brightly stained bone marrow‐derived macrophages whereas all the other mAb as well as normal rabbit antiserum gave no or negligible reactivity. Surface expression of the shared epitope is observed by day 3 of in vitro cultivation and markedly increased by interferon‐γ stimulation on day 9. Although hsp 60 is thought to be restricted to the mitochondrial compartment, antibody responses to this molecule have been implicated in autoimmunity. Our finding that bone marrow‐derived macrophages express a cross‐reactive epitope recognized by an mAb with specificity for amino acids 275 to 295 of the mycobacterial hsp 60 is consistent with such a role.
Recombinant 25‐kDa CD23 and interleukin 1α promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis
Authors: Liu Yong‐Jun , Cairns Jennifer A. , Holder Michelle J. , Abbot Sandra D. , Jansen Katherin U. , Bonnefoy Jean‐Yves , Gordon John , Maclennan Ian C. M. 
Published: March 2007

AbstractGerminal centers contain a proliferating pool of centroblasts which give rise to non‐dividing centrocytes. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescue. Rescue, in vivo, is likely to be dependent, initially, on interaction with antigen held on follicular dendritic cells (FDC). A subset of FDC located in that part of the germinal center furthest from centroblasts is particularly rich in CD23. Supernatants containing high levels of soluble CD23 were found not only to encourage the survival of germinal center B cells but also to promote their differentiation toward a plasmacytoid morphology; these activities were diminished following removal of CD23 from the supernatants. Recombinant 25‐kDa CD23 was initially found to be incapable of providing the signal for germinal center cell development but on the addition of interleukin 1α which, by itself, was inactive, rescue and differentiation of germinal center B cells were now achieved. Apoptosis in germinal center cells could also be prevented by the ligation of surface CD40 with monoclonal antibody: however, rescue via this pathway was not accompanied by plasmacytoid differentiation. These findings provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifurcation in the development of germinal center B cells following their rescue from apoptosis.