bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classical transplantation tolerance in the adult: the interaction between myeloablation and immunosuppression
Authors: Leong Louise Y. W. , Qin Shixin , Cobbold Stephen P. , Waldmann Herman 
Published: March 2007

AbstractAllogeneic bone marrow transplantation in the neonate is an effective way of inducing permanent tolerance to donor tissue. To do the same in the immunocompetent adult requires immunosuppression to counter host‐versus‐graft alloreactivity. Conditioning with monoclonal antibodies (mAb) to CD4 and CD8 has been sufficient where donor and recipient are mismatched at only multiple “minor” histocompatibility loci, or at major histocompatibility complex (MHC) class I plus “minor” loci, but not where the mismatch involves the entire MHC. Tolerance across the MHC barrier requires extra conditioning with agents that happen to be both immunosuppressive and myeloablative, so obscuring the assessment of which effect is important. By using dimethylmyleran as a selective “space”‐creating myeloablative agent, and CD4 plus CD8 mAb as sole immunosuppressive agents, we have been able to dissect the relative requirements for immunosuppression and myeloablation. We show here that transplantation tolerance could only be achieved when both types of agent were combined together so as to guarantee sufficient donor‐type hemopoietic chimerism. We argue that the donor marrow, given sufficient space, will engraft and provide a sustained source of tolerogen overriding any host resistance that antibodies cannot control.
Enhancement of CD3‐induced activation of human intestinal intraepithelial lymphocytes by stimulation of the β7‐containing integrin defined by HML‐1 monoclonal antibody
Authors: Sarnacki Sabine , Bè Bernadette , Buc Hélène , Le Deist Françoise , Cerf‐Bensussan Nadine 
Published: March 2007

AbstractIntraepithelial lymphocytes (IEL) form a large population of T cells in close contact with the intestinal lumen and differ from lymphocytes in other lymphoid compartments by their predominant CD8+ phenotype and the strong expression of the recently characterized β7‐containing integrin defined by the monoclonal antibody (mAb) HML‐1. The aim of the present in vitro study was to investigate the possible role of the integrin defined by HML‐1 in the activation of human IEL via the CD3‐T cell receptor (TcR) pathway.The proliferative response of IEL to optimal concentrations of immobilized OKT3 was found to be similar to that of peripheral blood lymphocytes enriched in CD8+ cells. When co‐immobilized with suboptimal concentrations of OKT3, antibodies directed against CD11a, CD29 and the β7‐containing integrin defined by HML‐1 exerted a strong synergistic effect on the proliferative response and on the expression of CD25 and CD71 antigens by human IEL. These data indicate that the CD3‐TcR pathway is functional in human IEL and contrast with previous observations suggesting that the CD3‐TcR pathway was difficult to elicit in human IEL. Furthermore, the present data show that the immune response of human IEL can be modulated via interactions between integrins expressed by IEL and their respective ligands in the mucosa and suggest that IEL's activation may depend on the level of expression of integrin ligands in the epithelium, particularly of the expression of the as yet unknown ligand for the IEL‐specific integrin defined by HML‐1.
Molecular analysis of anti‐idiotypic monoclonal antibodies in the HLA‐DR antigenic system
Authors: Armandola Elena A. , Mariani Sara M. , Zwickl Markus , Hardman Norman , Ferrone Soldano 
Published: March 2007

AbstractThe structural organization of anti‐idiotypic (id) antibodies has been investigated mostly in haptenic systems. No information is available about the structural characteristics of anti‐id antibodies in major histocompatibility complex (MHC) antigenic systems, although these data may contribute to our understanding of the molecular basis of their functional role in the immune response. Therefore, we have determined the nucleotide and derived amino acid sequence of the VH and VL regions of the anti‐id monoclonal antibodies (mAb) F5‐444, F5‐830, F5‐963, F5‐1126, F5‐1336 and F5‐1419, which had been elicited with the syngeneic anti‐HLA‐DR1, 4, w14, w8, 9 mAb AC1.59. The six anti‐id mAb are heterogenous in their VH and VL region gene usage. This structural heterogeneity is not correlated with their target specificity and with their ability to elicit anti‐HLA‐DR antibodies. The latter characteristic is markedly influenced by a limited number of amino acid substitutions, since mAb F5‐444, which induces anti‐HLA‐DR antibodies, differs only in two residues in complementarity‐determining regions and in five residues in framework regions from mAb F5‐1126, which does not induce anti‐HLA‐DR antibodies.The heterogeneity in VH and VL region gene usage by the six anti‐id mAb in the HLA‐DR system is at variance with the restricted VH and VL region gene usage by syngeneic anti‐id mAb in several haptenic systems. Furthermore, at variance with haptenic systems, the primary structure of the D segments of the anti‐id mAb is not correlated with their ability to induce anti‐HLA‐DR antibodies. On the other hand, the frequency of D‐D fusion events underlying the derivation of the D segments of the six anti‐id mAb in the HLA‐DR system and their average length are similar to those found in anti‐id mAb in haptenic systems. In addition, like in the latter systems, somatic mutations appear to contribute to the generation of diversity of anti‐id mAb in the HLA‐DR system.
In vivo production of interleukin‐10 by malignant cells in AIDS lymphomas
Authors: Emilie Dominique , Touitou Robert , Raphael Martine , Peuchmaur Michel , Devergnee Odile , Rea Delphine , Coumbraras Jean , Crevon Marie‐Claude , Edelman Lena , Joab Irène , Galanaud Pierre 
Published: March 2007

AbstractExpression of the interleukin (IL)‐10/BCRF1 gene was studied by in situ hybridization in tissue samples from acquired immunodeficiency syndrome (AIDS) lymphomas using a BCRF1 probe which also recognizes the human IL‐10 sequence. Hybridization was detected in 8 out of 15 lymphomas. In contrast, the IL‐10/BCRF1 gene expression was detected in only 1 out of 11 lymphomas from human immunodeficiency virus (HIV)‐seronegative patients (p = 0.05). In AIDS lymphomas, the number of cells labeled with a BCRF1‐specific probe was dramatically lower than that of cells labeled with the IL‐10/BCRF1 probe. Thus, the IL‐10 rather than the BCRF1 gene was expressed. Production of IL‐10 was associated with that of IL‐10 mRNA, as shown by immunodetection of the protein in numerous cells. In contrast, BCRF1‐producing cells were rarely detected. Both in situ hybridization and immunochemical experiments indicated that malignant cells were involved in this IL‐10 synthesis. IL‐10 production in AIDS lymphomas was associated with the presence of Epstein‐Barr virus (EBV) in lymphomatous cells (p = 0.02). As IL‐10 is a potent growth factor for human B lymphocytes, these results suggest that IL‐10 may stimulate the proliferation of malignant cells in an autocrine pathway in a number of AIDS lymphomas, and that EBV and HIV may synergistically trigger its production.
Expression of interleukin (IL)‐1β, IL‐6 and their respective receptors in the normal rat brain and after injury
Authors: Yan Hong Qu , Banos Miguel Alcaros , Herregodts Patrick , Hooghe Robert , Hooghe‐Peters Elisabeth L. 
Published: March 2007

AbstractThe expression of interleukin (IL)‐1β, IL‐6 and their respective receptors has been studied in the rat brain before and up to 24 h after injury. Messenger RNA transcripts of these four genes were detected by in situ hybridization (ISH) in different structures of the intact brain. The distribution was very similar for IL‐1β, IL‐6 and IL‐6 receptor (IL‐6R). The expression of IL‐1R was more widespread. Within hours after injury, an increased expression of IL‐1β, and thereafter of IL‐6 was documented. The expression of IL‐1R and IL‐6R was also increased. This expression was bilateral and not restricted to the injured area. Within 24 h, all ISH patterns had returned to normal. The molecular data were confirmed by protein data. Indeed, the distribution of IL‐6 (detected by immunocytochemistry) agreed with the ISH patterns for IL‐6. Furthermore, extracellular fluid was collected by microdialysis at the site of the lesion during 12 h and successive fractions were assayed for the presence of bioactive IL‐1 and IL‐6. Increases in IL‐1 and later in IL‐6 levels were detected. The rapid and concomitant increased expression of IL‐1β, IL‐6 and their receptors after injury stresses their possible early role in inflammatory mechanisms also in the brain, before any recruitment of inflammatory cells from remote nervous and not nervous areas.
Cloning and sequences of primate CD4 molecules: Diversity of the cellular receptor for simian immunodeficiency virus/human immunodeficiency virus
Authors: Fomsgaard Anders , Hirsch Vanessa M. , Johnson Philip R. 
Published: March 2007

AbstractTo study the interaction between the primate lentiviruses simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) and the CD4 receptor we have cloned and sequenced the CD4 molecule from six non‐human primate species: African green monkeys (three subspecies: sabeus, pytherethrus, aethiops), sooty mangabeys, patas monkeys, chimpanzees, rhesus macaques, and pig‐tail macaques. Molecular cDNA clones representing CD4 mRNA were generated from total RNA from peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) amplification including reverse transcriptase in initial reactions followed by two rounds of nested amplifications. Primer sequences were selected from regions conserved among human and rodent CD4 genes. Alignments of deduced amino acid sequences revealed interesting findings. First, all of the primate CD4 molecules were about 90% identical to the human CD4 sequence except the chimpanzee (98%). Second, two macaques or two African green monkey subspecies were as distanly related as the human versus chimpanzee sequences. Third, relatedness of CD4 sequences could not be predicted on the basis of geographic origin (Asian vs. African). Finally, upon sequencing several clones from individual monkeys, a low degree of sequence variation (nucleotide substitutions, deletions, and insertions) was found within the same animal, and in case of sooty mangabeys two distict populations of CD4 molecules were present within three of four individuals. The distinguishing features involved eight amino acid changes, including a single lysine deletion relative to a primate consensus sequence in the first complementary‐determing region of V1J1. These two CD4 populations were present also at the genomic DNA level and may arrive from the two chromosomal alleles, suggesting the existence of distinct sooty mangabey subspecies. Overall, the V1J1 and to a lesser extent V2J2 were the most variable regions among the sequences examined. By construction and expression in mammalian cell lines of CD4 chimeras in which these regions of the human CD4 were replaced by those of the African green monkey and pig‐tail macaques, a higher molecular mass of the CD4 chimeras were obtained in sodium dodecyl sulfate‐polyacrylamide gel electrophoresis suggesting that the additional N‐linked glycosylation sites present in these monkey CD4 are also used.
Selective and differential binding of interleukin (IL)‐1α, IL‐1β, IL‐2 and IL‐6 to glycosaminoglycans
Authors: Ramsden Lawrence , Rider Christopher C. 
Published: March 2007

AbstractThe binding of interleukin (IL)‐1α, IL‐1β, IL‐2 and IL‐6 to acidic polysaccharides was investigated by affinity chromatography of the recombinant, radioiodinated interleukins on columns of immobilized polysaccharide. Each interleukin showed selective binding retention. Overall heparin bound all four interleukins significantly, whereas chondroitin sulfate provided little retention. IL‐α and IL‐1β showed differential binding, with only the latter binding to hyaluronic acid. IL‐2 was virtually completely retained on fucoidan. Noniodinated recombinant IL‐2 bound similarly to fucoidan, and fucoidan was found to sequester IL‐2 activity in a bioassay employing IL‐2‐dependent CTLL cells. In all other cases tested, interleukin retention was partial, implying that interleukin binding sites are sparsely distributed along the polysaccharide chains. These findings suggest that during the immune response, interleukins will tend to be retained at sites of secretion by interaction with glycosaminoglycans in the extracellular matrix and on cell surfaces.
Anti‐tumor necrosis factor receptor and tumor necrosis factor agonist activity by an anti‐idiotypic antibody
Authors: Galloway Cynthia J. , Madanat Melanie S. , Sarr Timothy , Espevik Terje , Dumas Michael L. , Mitra George , Ranges Gerald E. 
Published: March 2007

AbstractTumor necrosis factor (TNF) is a cytokine which, among other properties, is a principle mediator of inflammation and septic shock. It acts upon target cells by binding to specific cell surface receptors. A10G10 is a murine monoclonal antibody which recognizes human TNF and neutralizes its activity. A rabbit polyclonal antibody directed at the antigen‐binding site of A10G10 was raised and affinity purified over an A10G10 column. The resultant anti‐idiotypic antibody recognized not only A10G10 but also both TNF receptors. It showed TNF agonist activity in two different TNF bioassays, and competed with several anti‐TNF receptor monoclonal antibodies and TNF itself for binding to cells. These results represent an example of a method for obtaining antibodies to a ligand‐specific receptor in the absence of the receptor itself.
In vivo priming of cytotoxic T lymphocyte responses in relation to in vitro up‐regulation of major histocompatibility complex class I molecules by short synthetic peptides
Authors: Zhou Xianzheng , Motal Ussama M. Abdel , Berg Louise , Jondal Mikael 
Published: March 2007

AbstractCytotoxic T lymphocytes (CTL) recognize target antigens as short peptides presented by major histocompatibility complex class I molecules (MHC‐I). Externally added peptides can sensitize target cells by binding directly to MHC‐I without any need for internal processing. Those which are similar in length to endogenously processed peptides are more potent in this respect than slightly longer peptides. Peptide MHC‐I interactions can also be reflected as upregulation of MHC‐I in vitro on certain cells. We have compared the capacity of Db, Kb‐ and Ld‐binding peptides, which are slightly different in length, to up‐regulate MHC‐I in vitro with their immunogenicity in vivo, in relation to generation of CTL responses. A clear correlation between these two different functions was found. We have also modified a 9‐mer Db‐binding peptide by adding cystein to the amino terminus and lysine to the amino‐ or carboxy terminus and studied the effects on MHC‐I up‐regulation and in vivo immunogenicity. Cystein and lysine contain reactive groups which are likely to influence the binding of modified peptides into the antigen‐binding groove of Db. These small modifications of the optimal 9‐mer peptide strongly influenced their functions but still there was a correlation between MHC‐I up‐regulation and CTL responses. Up‐regulation of MHC‐I in vitro may reflect a capacity of peptides to accumulate on the surface of particular antigen‐presenting cells in vivo.
Immunomodulation of streptococcal cell wall‐induced arthritis. Identification of inflammatory cells and regulatory T cell subsets by mercuric chloride and in vivo CD8 depletion
Authors: Van den Broek Maries F. , de Heer Emile , van Bruggen Mieke C. J. , de Roo Guido , Kleiverda Karin , Eulderink Frits , van den Berg Wim B. 
Published: March 2007

AbstractStreptococcal cell wall (SCW)‐induced arthritis is a chronic, erosive polyarthritis which can be induced in susceptible Lewis rats by one intraperitoneal injection of a sterile, aqueous suspension of SCW. The chronic phase of the disease is dependent on T cells. Mercuric chloride is an immunomodulating agent, causing autoimmunity in BN rats, but an OX8+ cell‐mediated immunosuppression in Lewis rats. Therefore, we investigated the effect of mercuric chloride, whether or not combined with in vivo OX8 depletion, on SCW‐induced arthritis in Lewis rats. We show that (a) depletion of OX8+ cells leads to a more chronic arthritis with a more rapid onset, (b) treatment with mercuric chloride induces a rapidly developing disease which is not chronic, and (c) treatment with mercuric chloride and OX8+ cell depletion induces an arthritis with a very rapid onset and enhanced chronicity. Together with histological data this suggests an important role for OX8+ T cells in controlling both the acute and chronic phase of the disease. In addition, mercuric chloride seems to induce an early activation of T cells resulting in an enhanced onset of disease, which is controlled later by enhanced activation of OX8+ cells.
T lymphocytes mediate immunologic control of C3 gene expression
Authors: Goldman Margaret B. , Knovich Mary Ann , Goldman John N. 
Published: March 2007

AbstractImmunologic control of C3 gene expression by tissue macrophages can be accomplished by treatment of spleen fragments with anti‐C3 antibody. We now demonstrate that suppression of C3 requires participation of T lymphocytes of both the CD4+ and CD8+ phenotypes. Pretreatment of splenic tissue with anti‐Thy‐1.2 monoclonal antibody blocks the ability of the anti‐C3 antibody to induce C3 suppression. Reduction in either the CD4+ or CD8+ subpopulations of T lymphocytes also abrogates C3 suppression demonstrating that both T cell subsets are required in addition to the inducing antibody. Artificially elevating intracellular levels of cAMP with cholera toxin can partially substitute for the effects mediated by T cells in this reaction. Therefore, normal expression of the C3 gene can be suppressed by a regulatory network that requires the presence of a specific inducing antibody and T lymphocytes of both the CD4+ and CD8+ subsets. This regulatory network has many similarities to regulatory networks that have been well documented in suppression of specific murine immunoglobulin allotypes.
Modulation of oral tolerance to ovalbumin by cholera toxin and its B subunit
Authors: Pierre Pascal , Denis Olivier , Bazin Hervé , Mbella Etondoh Mbongolo , Vaerman Jean‐Pierre 
Published: March 2007

AbstractOral administration to mice of ovalbumin (OVA), if given together with cholera toxin (CT) or its B subunit (CTB) prevented the hyporesponsiveness to OVA subsequently injected parenterally. Oral immunization with CT plus OVA or OVA plus CTB in fact primed the immune system, inducing a stronger response to a subsequent parenteral injection of OVA with complete Freund's adjuvant than in mice prefed only with OVA or with saline. Oral CT plus OVA also induced good serum IgG1 and IgA anti‐OVA responses, with slightly (not significant) decreased IgG2a and IgG2b responses. Our in vivo findings agree well with earlier in vitro data from others, including CT inhibition of the Th1 CD4+ T cell subset and with CT effect on B cells (induction of LPS‐stimulated IgM+ B cells to undergo increased switch differentiation to IgG1‐ and IgA‐secreting cells).
The role of natural antibodies and ABO (H) blood groups in transplantation of human lymphoid cells into mice
Authors: Huppes Wim , Paulonis John , Dijk Hans , Van Rooijen Nico , Van Bekkum Dirk W. 
Published: March 2007

AbstractRecently, evidence was presented that natural antibodies (NAb) are a crucial barrier to human cellular engraftment in severely immunosuppressed normal mice (Eur. J. Immunol. 1992.22:197.). In this report we show that normal mouse serum contains low titers of NAb against human cells of blood groups type O (H) and B and high titers against human cells of blood group A. Accordingly, human peripheral blood leukocytes (PBL) of group O (H) and B donors could be grafted successfully into normal BCBA mice (H‐2h/k) following irradiation with high dose total body irradiation (TBI). PBL of blood group type A donors did not engraft in normal mice but could be transplanted without difficulty in B cell‐deficient CBA/N mice which lack NAb, after conditioning with high dose TBI. Treatment of lethally irradiated normal BCBA mice with cobra venom factor (COF), which eliminates the third factor of complement, and liposomes containing dichloromethylene diphosphonate (C12DMP), which eliminates macrophages, resulted in engraftment of human blood group type A PBL. This implies that the NAb barrier for discordant xenogeneic cell transplantation can be abrogated.A method utilizing directly labeled probes and flow cytometry is described for the quantitation in mouse serum of NAb, reacting with human cells. Using sera of H‐2b/k mice we show that murine NAb react with human stem cells, granulocytes, lymphocytes and monocytes of blood group A and only weakly with similiar cells from blood group O (H) and B donors. Sera of H‐2b, H‐2d and H‐2k mice of different ages and microflora possess NAb against human erythrocytes of blood group type A and occasionally demonstrate weak titers against erythrocytes of blood groups B and O (H) and the Rhesus factor.
Cytokine regulation of the interleukin‐1 receptor antagonist protein in U937 cells
Authors: Berger Ann E. , Carter Donald B. , Hankey Susan O. , McEwan Robert N. 
Published: March 2007

AbstractA naturally occurring receptor‐level antagonist of interleukin‐1 (IRAPorIL‐1 ra) has recently been cloned. To determine what stimuli might regulate this inhibitor, cytokines were tested for their effects on the steady‐state level of IRAP mRNA in phorbol ester‐differentiated U937 cells. The cytokines tested fell into one of three groups: (a) inducers: granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), IL‐4, (b) weak inducers (<2‐fold stimulation): [IL‐lα, IL‐Iγ, and transforming growth factor‐β (TGF‐γ)] and (c) cytokines with no effect: (IL‐2, platelet‐derived growth factor, acidic fibroblast grouth factor, basic fibroblast growth factor, epidermal growth factor, granulocyte colony‐stimulating factor, IL‐3, IL‐5, IL‐6, interferon‐y, multi‐colony stimulating factor, tumor necrosis factor ‐a and IRAP itself. One hundred U/ml of either GM‐CSF or IL‐4 was the dose inducing peak IRAP mRNA expression; that peak expression occurred 12 h after addition of cytokine. GM‐CSF induced a 34 ±15‐fold increase in IRAP mRNA, and IL‐4 induced a 15± 6‐fold increase. In the same RNA samples, GM‐CSF increased IL‐ip mRNA 5.9 ± 1.7‐fold, but IL‐4 decreased IL‐Iγ mRNA to half that of control levels (0.45 ± 0.17). Thus, a single stimulus (IL‐4) decreased the expression of an agonist (IL‐1) while it increased the expression of an antagonist (IRAP). When U937 cells were treated with both IL‐4 and GM‐CSF, the level of IRAP mRNA induced was additive, suggesting that the cytokines acted differently to increase IRAP mRNA levels. The level of IL‐1 mRNA in cells treated with both IL‐4 and GM‐CSF was intermediate. Dexamethasone and cycloheximide inhibited all mRNA increases and did not reverse IL‐4‐induced decreases in IL‐1 mRNA. These studies have identified two cytokines which induce IRAP in the monocytic cells studied, and have partially characterized the differential regulation of IL‐1 and its antagonist, IRAP.