bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of interleukin‐10 production by β‐adrenergic agonists
Authors: Suberville Sidonie , Bellocq Agnès , Fouqueray Bruno , Philippe Carole , Lantz Olivier , Perez Joëlle , Baud Laurent 
Published: March 2007

AbstractCatecholamines have been shown to inhibit some aspects of macrophage activation through a β receptor‐dependent mechanism. This study was undertaken to analyze the effects of isoproterenol, a specific β‐adrenergic agonist, on the synthesis of interleukin‐10 (IL‐10), a major macrophage‐deactivating factor. Isoproterenol increased IL‐10 release from lipopolysaccharide‐(LPS)‐activated mouse peritoneal macrophages in a dose‐dependent manner. A significant effect was already observed with 1 μM isoproterenol, while a 4.5‐fold increase was achieved with 10 μM. This increase was observed only if macrophages were exposed to isoproterenol for at least 2 h before LPS challenge. It was apparent within 0.5 h and persisted through 24 h at all the LPS concentrations used. A similar increase was observed at the IL‐10 mRNA level, as judged by enzyme‐linked immunosorbent assay‐polymerase chain reaction. The macrophage response to isoproterenol that led to cyclic AMP accumulation was markedly inhibited by H‐89, a potent inhibitor of protein kinase A. These data suggest the involvement of cyclic AMP in the regulation of IL‐10 synthesis by isoproterenol. IL‐10 was in turn partly responsible for a reduction in tumor necrosis factor‐α synthesis. In vivo, the administration of oxprenolol, a β‐receptor antagonist, significantly reduced serum IL‐10 levels 90 min after LPS challenge. Thus, the present study provides the first evidence that endogenous catecholamines are of critical importance in determining the magnitude of the IL‐10 response in experimental endotoxemia.
A wild‐type p53 cytotoxic T cell epitope is presented by mouse hepatocarcinoma cells
Authors: Lacabanne Valérie , Viguier Mireille , Guillet Jean‐Gérard , Choppin Jeannine 
Published: March 2007

AbstractThe possibility to identify epitopes presented by tumor cells to cytotoxic T lymphocytes (CTL) has given rise to new fields in tumor immunology. The tumor suppressor gene product p53 is a good candidate antigen because it is involved in the tumorigenesis of many cancers. It accumulates in an inactivated form due to mutation or formation of heterodimers with an oncogene product. Epitopes from the mutant or wild‐type p53 proteins are thought to be presented by tumor cells and to induce a tumor‐specific CTL response. To identify such epitopes, mouse wild‐type p53 peptides encompassing the H‐2 Db anchoring motif were tested for their association with the Db molecule. Positive peptides were assayed for their ability to induce CTL in C57BL/6 mice. CTL specific for one wild‐type p53 peptide, p232–240, were isolated and found to lyse hepatocarcinoma cell lines established from mice transgenic for simian virus 40 large T antigen which overexpress p53. These results show that the p232–240 epitope from wild‐type p53 is naturally processed and presented in H‐2b tumor cells.
Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma
Authors: Bogen Bjarne 
Published: March 2007

AbstractTumors could escape an immune attack by inducing peripheral T cell tolerance. To test this, T cell receptor (TCR)‐transgenic mice were injected with plasmacytoma cells secreting a highly tumor‐specific antigen, a monoclonal immunglobulin (Ig), for which the transgene‐encoded TCR is specific. The TCR recognizes a third hypervariable region idiotypic (Id) peptide of the Ig, presented by a class II molecule on host antigen‐presenting cells. The TCR‐transgenic mice have previously been shown to be protected against an Id+ plasmacytoma challenge. In the present experiments, the protection was deliberately overwhelmed by subcutaneous injection of large numbers of plasmacytoma cells. Such tumor mice, chronically exposed to increasing amounts of monoclonal Ig, delete Id‐specific CD4+ T cells in their peripheral lymphoid organs and in the tumor. The residual CD4+ cells express endogenous, rather than transgene‐encoded TCR α chains. Peripheral deletion, functional T cell unresponsiveness, and thymocyte deletion are all first detected at the same serum concentration of monoclonal Ig, ∼50 μg/ml (0.3 μM), and become more and more profound as the tumor burden increases. The results suggest that peripheral T cell tolerance to Id could be a tumor escape mechanism in patients with B cell malignancies. In addition, the findings have implications for T cell tolerance to Ig V regions in normal individuals.
Conservation of minor histocompatibility antigens between human and non‐human primates
Authors: den Haan Joke M. M. , Bontrop Ronald E. , Pool Jos , Sherman Nicholas , Blokland Els , Engelhard Victor H. , Hunt Donald F. , Goulmy Els 
Published: March 2007

AbstractIt is well accepted that minor histocompatibility antigens (mHag) can function as transplantation barriers between HLA‐matched individuals. Little is known about the molecular nature and evolutionary conservation of mHag. It is only very recently that the first human mHag were identified. The HLA‐A2.1‐restricted mHag HA‐2 and the HLA‐B7‐restricted mHag H‐Y appeared to be peptides derived from polymorphic self proteins. Here we show that the HLA‐A2.1‐restricted mHag HA‐1, HA‐2, and the H‐Y peptides are conserved between man, chimpanzees and rhesus macaques. Human cytotoxic T cell clones specific for the HLA‐A2.1‐restricted mHag HA‐1, HA‐2, and H‐Y recognized HLA‐A2.1 gene‐transfected chimpanzee and rhesus macaque cells. Highpressure liquid chromatography fractionation of HLA‐A2.1‐bound peptides isolated from the HLA‐A2.1‐transfected chimpanzee cells revealed that the chimpanzee HA‐1 and HA‐2 co‐eluted with the human HA‐1 and HA‐2. Subsequent amino acid sequencing showed that the chimpanzee HA‐2 peptide is identical to the human HA‐2 peptide. Our functional and biochemical results demonstrate that mHag peptides are conserved for over 35 million years.
Induction of CD14 expression in Lpsn, Lpsd and tumor necrosis factor receptor‐deficient mice
Authors: Takakuwa Tetsuya , Knopf Hans‐Peter , Sing Andreas , Carsetti Rita , Galanos Chris , Freudenberg Marina A. 
Published: March 2007

AbstractThe involvement of CD14 in lipopolysaccharide (LPS) recognition and signaling has been demonstrated in several studies. For this reason, we investigated whether the resistance of Lpsd mice to LPS might be related to an impaired CD14 expression. We compared the in vivo and in vitro expression of CD14 in Lpsn (LPS sensitive) and Lpsd mice, and its modulation by LPS, killed gramnegative and gram‐positive bacteria and double‐stranded (ds)RNA. Untreated Lpsn and Lpsd cultured macrophages (MΦ), expressed similar amounts of CD14 mRNA and membrane‐bound (m)CD14. LPS enhanced CD14 expression only in Lpsn MΦ, while all bacteria, or dsRNA, enhanced CD14 in Lpsn and Lpsd MΦ. Similarly, in vivo administration of LPS induced or enhanced CD 14 mRNA in different organs of Lpsn mice only, while bacteria or dsRNA in both types of mouse. Furthermore, exogenous recombinant tumor necrosis factor (TNF) induced in vivo and in vitro enhanced CD 14 expression in Lpsn, Lpsd and also in TNF receptor 2‐deficient (TNFR2−/−) mice, but failed to do so in TNFR1−/− mice, showing that TNFR1 mediates the effect of TNF on CD14. However, LPS, bacteria and dsRNA induced CD14 in both TNFR2−/− and TNFR1−/− mice to a similar extent, revealing that this induction does not require TNF signaling.
Immunodominance of cytotoxic T lymphocyte epitopes co‐injected in vivo and modulation by interleukin‐12
Authors: Eberl Gérard , Kessler Benedikt , Eberl Lucie Peduto , Brunda Michael J. , Valmori Danila , Corradin Giampietro 
Published: March 2007

AbstractImmunodominance (ID) of T cell epitopes is a well‐documented phenomenon that might have profound significance in the evolution of T cell responses to pathogens, tumors, autoantigens and vaccines. With the intention of developing vaccines composed of several cytotoxic T cell (CTL) epitopes, we injected mice with peptide mixtures containing two to five CTL epitopes and observed clear patterns of ID. In a first case, ID strictly correlated with the competitor activity of the individual peptides for H‐2Kd, whereas in a second case, the absence of correlation between ID and competitor activity, binding affinity, half‐life of the peptides in serum, induction of proliferation in vitro and the individual immunogenicity of the peptides, suggested to us that ID of co‐injected CTL epitopes can be determined both at the peptide level (binding affinity to H‐2Kd) and at the T cell level. This hypothesis is supported by our finding that interleukin‐12 strongly modulates ID when it is not correlated with MHC binding.
Differential regulation of interleukin‐12‐and interleukin‐15‐induced natural killer cell activation by interleukin‐4
Authors: Salvucci Ombretta , Mami‐Chouaib Fathia , Moreau Jean Louis , Thèze Jacques , Chehimi Jihed , Chouaib Salem 
Published: March 2007

AbstractThe regulation of human natural killer (NK) cell activation is under the control of a network of regulatory signals provided by cytokines. In the present study, we investigated the functional interaction between interleukin (IL)‐4 and two monocyte/macrophage‐derived cytokines, IL‐12 and IL‐15, during the process of NK stimulation. Using freshly isolated human NK cells, we have demonstrated that IL‐4 negatively regulates lymphokine‐activated killer (LAK) activity induced by IL‐15 against the NK‐resistant Daudi target cells. In contrast, IL‐4 had no effect on IL‐12‐stimulated LAK generation. The differential effect of IL‐4 on NK cell activation by IL‐12 and IL‐15 correlates with its ability to increase or to down‐regulate the level of tumor necrosis factor‐α and interferon‐γ release by NK cells, respectively. In contrast, endogenous transforming growth factor‐β1 does not appear to be involved in the IL‐4 regulatory pathway. Furthermore, while IL‐4 was found to decrease the basal expression of the IL‐2 receptor β subunit utilized by IL‐15, it had no effect on the expression of the β1 chain of the IL‐12 receptor compared to untreated cells. Northern blot analysis indicated that the IL‐4 regulatory effect on NK lytic function was associated with its capacity to down‐regulate granzyme B and perforin gene transcription in response to IL‐15 and its failure to affect the expression of both gene's in response to IL‐12. Together, these data suggest the existence of a distinct cross‐talk between IL‐4 and IL‐15 or IL‐12 signaling pathways during the regulation of human non‐major histocompatibility complex‐restricted cytotoxicity.
Autoimmune disease of exocrine organs in immunodeficient alymphoplasia mice: a spontaneous model for Sjören's syndrome
Authors: Tsubata Rieko , Tsubata Takeshi , Hiai Hiroshi , Shinkura Reiko , Matsumura Ryutaro , Sumida Takayuki , Miyawaki Shigeki , Ishida Hiroshi , Kumagai Shunichi , Nakao Kazuwa , Honjo Tasuku 
Published: March 2007

AbstractMice homozygous for an autosomal recessive mutation aly (alymphoplasia) lack both lymph nodes and Peyer's patches, and show defects in both humoral and cellular immunity. Histopathological analysis revealed chronic inflammatory changes in exocrine organs such as the salivary gland, lacrimal gland, and pancreas of the homozygotes (aly/aly), but not the heterozygotes (aly/+). In these exocrine organs, mononuclear cells consisting mainly of CD4+ T cells infiltrate periductal areas, and, in some cases, the cell infiltration extended to lobules. The inflammatory changes in exocrine organs were transferred by a T cell‐enriched fraction of spleen cells from homozygous animals. These results suggest that autoimmune mechanisms mediated by self‐reactive T cells may be involved in the inflammatory lesions of various exocrine organs in the homozygous mice, although these mice show immunodeficiency. Inflammatory changes were also observed in the lung of the homozygotes. Since Sjögren's syndrome is characterized by diffuse lymphocyte infiltration in the periductal areas of the lacrimal and salivary glands and is occasionally associated with pulmonary disease, aly/aly mice may serve as a unique spontaneous model of Sjögren's syndrome.
Thymocyte differentiation in γ‐irradiated severe‐combined immunodeficient mice: characterization of intermediates and products of V(D)J recombination at the T cell receptor α locus
Authors: Zhu Chengming , Bogue Molly A. , Roth David B. 
Published: March 2007

AbstractTreatment with DNA‐damaging agents promotes rescue of V(D)J recombination, limited thymocyte differentiation, and development of thymic lymphomas in severe‐combined immunodeficient (SCID) mice. One intriguing aspect of this system is that irradiation rescues rearrangements at the T cell receptor (TCR) β, γ and δ loci, but not at the TCR α locus. Current models posit that only those loci that are recombinationally active at the time of irradiation can be rescued. Here, we employ sensitive, semiquantitative ligation‐mediated polymerase chain reaction assays to detect a specific class of recombination intermediates, hairpin coding ends, at the TCR α locus. We found that Jα‐coding ends are undetectable in unirradiated SCID thymocytes, but accumulate after irradiation at times coincident with the emergence of a CD4+CD8+ thymocyte population. Coding joints produced by joining of these ends, however, are extremely rare. To test whether the presence of hairpin coding ends at TCR α is sufficient for irradiation‐mediated rescue of coding joint formation, we administered a second dose of γ‐irradiation after abundant CD4+ CD8+ thymocytes and hairpin TCR α coding ends had accumulated. This treatment failed to stimulate rescue of TCR α coding joints. Thus, the presence of hairpin coding ends at the time of irradiation, while perhaps necessary, is not sufficient for rescue of V(D)J rearrangements. These results support a refined model for irradiation‐mediated rescue of TCR rearrangements in SCID mice.
Major histocompatibility complex and T cell receptor interaction of the P91A tum− peptide
Authors: McCormick David , Stauss Hans J. , Thorpe Christopher , Travers Paul , Dyson P. Julian 
Published: March 2007

AbstractThe P91A antigen was identified following mutation of P1 mastocytoma cells. The peptide epitope is encoded by a mutant form of the S3 subunit of the PA 700 proteasome regulatory complex. P91A stimulates a strong CD8+ T cell response when expressed on tumor cells or normal tissue and P91A‐specific T cells express a restricted range of T cell receptors. Although it is a strong Ld‐binding peptide, P91A does not conform to the established motif for this major histocompatibility complex (MHC) molecule and this has hampered elucidation of the precise epitope. Ld predominantly associates with nonamer peptides; however, using a variety of complementary approaches, the P91A epitope is identified as the octamer QNHRALDL. In the absence of the Ld motif residue proline at position 2, residues 5–7 are primarily involved in MHC interaction. P91A is thus atypical in its interaction with Ld. Residues 1, 3, and 4 are found to influence T cell recognition of P91A. Definition of the P91A peptide will allow studies on P91A processing and interactions of the P91A peptide/MHC complex with T cell receptors of differing avidity to establish the basis for restricted T cell receptor usage. The basis for the failure of the P91A tum+ peptide (QNRRALDL) to bind to Ld is addressed by molecular modeling.
Transgene‐encoded human CD2 acts in a dominant negative fashion to modify thymocyte selection signals in mice
Authors: Melton Elizabeth , Sarner Nitza , Torkar Michaela , van der Merwe P. Anton , Russell Jennifer Q. , Budd Ralph C. , Mamalaki Clio , Tolaini Mauro , Kioussis Dimitris , Zamoyska Rose 
Published: March 2007

AbstractCD2 is a cell surface glycoprotein present on all T cells which has been shown to function as an adhesion and signaling molecule. Expressed early in T cell development, human CD2 (HCD2) has been suggested to play a role during thymopoiesis. However, the relevance of CD2 in T cell development has been called into question recently, as neither disruption of the CD2 gene nor anti‐CD2 antibody treatment of fetal thymic organ cultures in mouse were shown to have any discernible consequences. We have expressed HCD2 at high levels in transgenic mice and found a profound effect of the transgene on thymocyte differentiation. Transgenic thymuses are considerably reduced in cell number as a consequence of increased apoptosis of double‐positive (DP) thymocytes in the cortex. The remaining DP cells have up‐regulated levels of T cell receptor (TCR) and are resistant to apoptosis mediated by administration of antigen. These effects are dependent on the cytoplasmic domain of HCD2, as mice expressing comparable levels of a tailless HCD2 transgene have a normal phenotype. The HCD2 cytoplasmic domain contains several regions of identity with mouse CD2 and can interact effciently with mouse intracellular signaling machinery. These results suggest there is considerable cross‐talk between CD2 and TCR on developing thymocytes with consequences for the stimulation threshold of mature T cells.
Human antibodies from phage libraries: neutralizing activity against human immunodeficiency virus type 1 equally improved after expression as Fab and IgG in mammalian cells
Authors: Samuelsson Astrid , Yari Fayezeh , Hinkula Jorma , Ersoy Oguz , Norrby Erling , Persson Mats A. A. 
Published: March 2007

AbstractHuman antibodies against HIV‐1 have been sought to study neutralization events on the molecular level, and for possible use in passive immune intervention. The development of phage display techniques has opened the possibility of rapidly generating human monoclonal antibodies with desired specificities. We and others have isolated human HIV‐1 neutralizing antibody fragments using this technique. Bacterial expression of isolated clones does, however, differ broadly both in expression levels and functional activity. In addition, intact IgG cannot be expressed in bacteria. By transferring the genes of isolated Fab clones to a mammalian expression system we could perform a comparison of functional activity between Fab expressed in bacterial and mammalian cells, as well as Fab and whole IgG. Fab fragments expressed in mammalian cells showed increased virus neutralizing activity compared to the same Fab clones expressed in Escherichia coli, underlining the inefficiency of procaryotic expression. No difference in HIV‐1 neutralizing capacity was detected between monovalent (Fab) and divalent (whole antibody) reagents expressed in CHO cells. Thus, bivalency does not always confer improved neutralization efficacy.
The development of IgE+ memory B cells following primary IgE immune responses
Authors: Le Gros Graham , Schultze Nathalie , Walti Simone , Einsle Karin , Finkelman Fred , Kosco‐Vilbois Marie H. , Heusser Christoph 
Published: March 2007

AbstractWe studied whether long‐lived IgE+ memory B cells develop following three types of primary IgE immune responses. Immunization of mice with anti‐IgD antibody induced a T cell‐dependent, interleukin (IL)‐4‐dependent primary IgE response and the formation of IgE isotype switched (IgE+) memory B cells. These IgE+ memory B cells could be stimulated in vivo by injection with goat anti‐IgE antibodies to produce a profound IL‐4‐independent memory IgE response. By contrast, both infection of mice with Nippostrongylus brasiliensis or repeated immunization with benzylpenicilloyl‐keyhole limpet hemocyanin (BPO‐KLH) in alum stimulated good primary IgE responses and profound memory T cell‐dependent antigen‐specific IgE responses, but failed to induce the development of long lived IgE+ memory B cells because they could not be recalled with goat anti‐IgE antibodies. Mice receiving double immunizations combining anti‐IgD with either N. brasiliensis infection or BPO‐KLH immunization mounted significant goat anti‐IgE‐induced secondary IgE responses, but no N. brasiliensis or BPO‐KLH‐specific IgE could be detected. This indicates that the N. brasiliensis and BPO‐KLH induced immune responses do not suppress the development of IgE+ B cells, but rather, do not provide the necessary conditions for their formation. Taken together these data indicate that long‐lived IgE+ B cells fail to develop during the primary IgE response to N. brasiliensis infection or BPO‐KLH immunization. By contrast, significant numbers of IgE+ memory B cells form during the primary IgE immune response induced by anti‐IgD immunization. Our observations suggest that immunization protocols involving membrane IgD cross‐linking and limited duration of cognate T cell help are necessary for the formation of IgE+ memory B cells. It will be important to determine the relevance of membrane IgD interaction with allergens, as this would influence the design of new therapies for the treatment of allergy and asthma.
CD40 engagement induces monocyte procoagulant activity through an interleukin‐10 resistant pathway
Authors: Pradier Olivier , Willems Fabienne , Abramowicz Daniel , Schandené Liliane , De Boer Mark , Thielemans Kris , Capel Paul , Goldman Michel 
Published: March 2007

AbstractInteractions between membrane‐bound molecules were previously shown to be involved in the induction of tissue factor‐dependent monocyte procoagulant activity (PCA) by activated T cells. To investigate the potential role of the CD40/CD40 ligand (CD40L) pathway in this process, we first determined the effects of blocking anti‐CD40 or anti‐CD40L monoclonal antibodies (mAb) on the development of monocyte PCA during mixed lymphocyte reaction (MLR) between allogeneic peripheral blood mononuclear cells (PBMC). The strong inhibitory effect exerted by both mAb (mean percentages of inhibition: 88 and 91% for anti‐CD40 and anti‐CD40L mAb, respectively) indicates that CD40/CD40L interactions are required for the induction of PCA in MLR. These data led us to measure monocyte PCA after incubation of PBMC or purified monocytes with a stimulating anti‐CD40 mAb (BL‐C4) or with 3T6 fibroblasts transfected with the gene encoding CD40L. In both systems, we found that CD40 engagement strongly induced monocyte PCA which was related to tissue factor expression as shown by flow cytometric analysis. Finally, we observed that recombinant interleukin (IL)‐10, which inhibits lipopolysaccharide‐induced PCA, did not significantly influence CD40‐dependent PCA. We conclude that CD40 engagement on monocytes induces tissue factor‐dependent PCA through an IL‐10‐resistant pathway. These findings have implications for the control of coagulation events triggered by interactions between T cells and monocytes.
The canonical T cell receptor of dendritic epidermal γδ T cells is highly conserved between rats and mice
Authors: Kühnlein Petra , Mitnacht Rita , Torres‐Nagel Nora E. , Herrmann Thomas , Elbe Adelheid , Hünig Thomas 
Published: March 2007

AbstractTwo monoclonal antibodies with specificity for rat γδ T cell receptor (TCR) were generated. One, called V65, reacts with all CD3+ αβ TCR− rat T cells and thus recognizes a constant determinant of the rat γδ TCR (Kühnlein et al., Journal of Immunology 1994, 153: 979). The other, called V45, reacts with approximately 80% of γδ T cells in peripheral lymphoid organs. In rat epidermis, V65 but not V45 detects a dense network of the dendritic epidermal T cells (DETC). Analysis of epidermal RNA by polymerase chain reaction (PCR) indicated that Vγ3 and Vδ1 are the predominant, if not exclusive TCR V transcripts present at this site. Sequence analysis of cDNA clones obtained by reverse transcription‐PCR with Vγ3‐ and Vδ1‐specific primers revealed that the variable domains of rat DETC γ and δ chains are very homologous to those described in mice (92 % and 95 % identity at the protein level). The complete conservation between the two species of the amino acid sequences at the V‐(D)‐J transitions of this monomorphic receptor indicates that the interaction of the DETC TCR with its as yet unknown ligand must be of central importance for DETC function.