bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptides derived from the whole sequence of BCR‐ABL bind to several class I molecules allowing specific induction of human cytotoxic T lymphocytes
Authors: Buzyn Agnès , Ostankovitch Marina , Zerbib Anne , Kemula Mathilde , Connan Francine , Varet Bruno , Guillet Jean‐Gérard , Choppin Jeannine 
Published: March 2007

AbstractChronic myeloid leukemia (CML) is characterized cytogenetically by a t(9;22) translocation which generates a hybrid bcr‐abl gene, encoding a p210bcr‐abl fusion protein. The induction in vitro of leukemia‐specific T cells reactive with p210bcr‐abl is a strategy developed for an immunological therapeutic approach in CML. Peptides from the junction region of this chimeric protein have been considered as potential targets for a cytotoxic response against leukemic cells. However, only a few peptides encompassing the two p210bcr‐abl breakpoints have been shown to bind to the most common HLA class I molecules, which limits the number of patients who could benefit from this approach. We assume that the presence of chimeric BCR‐ABL protein in leukemic cells may affect processing and delivery of peptides, possibly giving rise to new epitopes at the cell surface. We selected 162 peptides from the whole sequence of this protein, including 14 peptides of the b2a2 and b3a2 junctions, which had an anchor motif for a common HLA class I molecule. We tested their ability to bind to eight HLA class I molecules (HLA‐A1, ‐A2, ‐A3, ‐A11, ‐B7, ‐B8, ‐B27, ‐B44). We identified 48 peptides from outside the junction region, with intermediate or strong binding capacities to these HLA class I molecules contrasting with only six junction peptides with a moderate binding capacity to HLA‐A3/A11, ‐B8, or ‐B44 molecules. Moreover, cytotoxic T lymphocyte lines specific for various peptides outside the junction were generated from peripheral blood mononuclear cells of HLA‐A2 or ‐B7 healthy donors and from one CML patient. These results contribute to evaluation of immunity to the BCR‐ABL chimeric protein. Further studies are required to investigate whether such epitopes are correctly processed and presented by leukemic cells.
Molecular characterization of a gene in the rat homologous to human CD94
Authors: Dissen Erik , Berg Siri F. , Westgaard Ingunn H. , Fossum Sigbjørn 
Published: March 2007

AbstractThree classes of major histocompatibility (MHC) class I binding receptors on natural killer (NK) cells have so far been described: CD94/NKG2 heterodimeric receptors and killer cell inhibitory receptors in the human, and Ly‐49 homodimers in rodents. CD94, NKG2 and Ly‐49 belong to the C‐type lectin super‐family. As yet, CD94 and NKG2 molecules have not been detected in rodents or Ly‐49 in humans. It has therefore been proposed that the two receptors represent functional equivalents in these species. The present study describes the cDNA cloning of a novel rat gene encoding a protein of 179 amino acids, 54.2 % identical to human CD94. The single‐copy Cd94 gene is localized to the rat NK gene complex (NKC), within 50 kb from Nkrp2, between the Nkrp1 and Ly49 gene clusters. By Northern blot analysis, we showed that rat CD94 is selectively expressed by NK cells and a small subset of T cells, similar to the human ortho‐logue. This expression is strain dependent, with high expression in DA NK cells and low in PVG NK cells. Evidence is presented that this difference is not due to receptor repertoire shaping by MHC‐encoded ligands, but is controlled by genetic elements residing within the NKC. The identification of a rat CD94 orthologue suggests that NK cell populations utilize two different C‐type lectin receptors for MHC class I molecules in parallel.
Two separable T cell receptor signals reconstitute positive selection of CD4 lineage T cells in vivo
Authors: Schmitt Steffen , Müller Klaus‐Peter , Kyewski Bruno A. 
Published: March 2007

AbstractPositive selection is an obligatory step during intrathymic T cell differentiation. It is associated with rescue of short‐lived, self major histocompatibility complex (MHC)‐restricted thymocytes from programmed cell death, CD4/CD8 T cell lineage commitment, and induction of lineage‐specific differentiation programs. T cell receptor (TCR) signaling during positive selection can be closely mimicked by targeting TCR on immature thymocytes to cortical epithelial cells in situ via hybrid antibodies. We show that selection of CD4 T cell lineage cells in mice deficient for MHC class I and MHC class II expression can be reconstituted in vivo by two separable T cell receptor signaling steps, whereas a single TCR signal leads only to induction of short‐lived CD4+CD8la intermediates. These intermediates remain susceptible to a second TCR signal for 12‐48 h providing an estimate for the duration of positive selection in situ. While both TCR signals induce differentiation steps, only the second one confers long‐term survival on immature thymocytes. In further support of the two‐step model of positive selection we provide evidence that CD4 T cell lineage cells rescued by a single hybrid antibody pulse in MHC class II‐deficient mice are pre‐selected by MHC class 1.
Biologically active, alternatively processed interleukin‐1β in psoriatic scales
Authors: Lundqvist Elisabet Nylander , Egelrud Torbjörn 
Published: March 2007

AbstractThe aims of the present work were to elucidate the biochemical properties of interleukin‐1β (IL‐1β) in psoriatic scales to get information on the processing of epidermal IL‐1β in psoriasis, and to elucidate whether the IL‐1β in psoriatic scales possesses biological activity. By means of ion exchange chromatography, IL‐1β in extracts of psoriatic scales was purified to a stage where it could be analyzed with electrophoretic methods and immunoblotting. Compared to mature recombinant human IL‐1β (Ala 117 IL‐1β), IL‐1β in psoriatic scales had a slightly higher apparent molecular mass and a more acidic isoelectric point, as revealed by two‐dimensional electrophoresis under denaturing conditions. Isoelectric focusing under non‐denaturing conditions of IL‐1β partially purified from psoriatic scales, or from non‐inflamed plantar stratum corneum (Nylander Lundqvist, E., Bäck, O. and Egelrud, T., J. Immunol. 1996. 157: 1699), and of mature IL‐1β, followed by immunoblotting with IL‐1β‐specific antibodies, showed that psoriatic scales contained two components with IL‐1β‐like immuno‐reactivity which were isoelectric at pH 6.1 and 6.3, respectively. Theses components could also be detected in extracts of plantar stratum corneum, which also contained small amounts of an IL‐1β‐like component isoelectric at pH 6.9. Mature IL‐1β was isoelectric at pH 6.9. No IL‐1β‐like biological activity could be detected in crude extracts of psoriatic scales. These extracts also contained high amounts of IL‐1 receptor antagonist. Partially purified preparations of IL‐1β from psoriatic scales, in which an apparently total separation of IL‐1β and IL‐1 receptor antagonist had been achieved, could induce expression of E‐selectin in human umbilical vein endothelial cells. This activity was inhibited by antibodies specific for IL‐1β, but not by antibodies specific for IL‐1α. It is concluded that psoriatic scales contain biologically active IL‐1β, which has been processed by a mechanism which may be similar to that present in non‐inflamed plantar stratum corneum, and which does not involve IL‐1β converting enzyme.
Interleukin‐2 receptor β and γ chain dysregulation during the inhibition of CD4 T cell activation by human immunodeficiency virus‐1 gp120
Authors: Bani Lynda , David Denis , Février Michèle , Pialoux Gilles , Dupont Bertrand , Sugamura Kazuo , Thèze Jacques 
Published: March 2007

AbstractWe have observed that CD4 T lymphocytes from human immunodeficiency virus (HIV)‐infected patients marginally express interleukin‐2 receptor (IL‐2R)β and IL‐2Rγ chains which are essential for IL‐2 signal transduction. To analyze this observation further, we studied the influence of gp120 on the cell surface expression of IL‐2Rβ and IL‐2Rγ by purified CD4 lymphocytes in vitro. Cross‐linking of the T cell receptors of these lymphocytes initiates entry into the cell cycle as measured by CD69 and CD71 cell surface expression and [3H]thymidine incorporation. It also induces the cell surface expression of IL‐2Rβ and IL‐2Rγ. We have shown that treatment of the CD4 T lymphocytes with HIV‐1 gp120 before anti‐CD3 stimulation impedes cell cycle progression as measured by reduced CD71 expression and inhibition of [3H]thymidine incorporation. Furthermore, cell surface expression of IL‐2Rβ and IL‐2Rγ subunits, which form the functional intermediate‐affinity IL‐2R, are significantly inhibited. More importantly, addition of exogenous IL‐2 does not restore the proliferation of the CD4 T cells treated with gp120, suggesting that cells are anergic and/or that the remaining IL‐2R are not functional. This is the first study of IL‐2Rβ and IL‐2Rγ dysregulation in the context of HIV infection and shows that CD4 is also involved in IL‐2R expression.
Enhanced sensitivity of P‐glycoprotein‐positive multidrug resistant tumor cells to complement‐mediated lysis
Authors: Bomstein Yonit , Fishelson Zvi 
Published: March 2007

AbstractThe interaction of KB‐V1, a multidrug resistant (MDR) variant of the KB‐3–1 human oral carcinoma, with human complement was investigated. KB‐V1 cells were found to be more sensitive than KB‐3–1 cells to complement‐mediated lysis. Detailed analysis of the capacity of KB cells to activate human complement demonstrated that both C3b deposition and formation of the membrane attack complex (MAC) are higher on KB‐V1 than on KB‐3–1 cells. Furthermore, the MAC formed on KB‐V1 cells, but not on KB‐3–1 cells, was found to be resistant to trypsin treatment, i.e. more stably inserted into the plasma membrane. Immunofluorescence analysis by flow cytometry showed that KB‐V1 cells express less decay‐accelerating factor (DAF, CD55) than KB‐3–1 cells. Two other complement regulatory proteins, membrane cofactor protein (MCP, CD46) and CD59 are expressed to a similar extent on both KB‐V1 and KB‐3–1 cells. Treatment of KB‐V1 cells with neutralizing anti‐P‐glycoprotein (P‐gp) monoclonal antibodies reduced their sensitivity to complement. In addition, KB‐V1 revertants which cease to express P‐gp become more resistant to complement. These results indicate that multiple factors, such as reduced expression of DAF, enhanced deposition of C3b and increased binding and stability of the MAC may contribute to the increased complement sensitivity of KB‐V1 cells. It is suggested that P‐gp is responsible for the complement‐sensitive phenotype of KB‐V1 cells.
A filarial cysteine protease inhibitor down‐regulates T cell proliferation and enhances interleukin‐10 production
Authors: Hartmann Susanne , Kyewski Bruno , Sonnenburg Bettina , Lucius Richard 
Published: March 2007

AbstractFilarial nematodes are a cause of chronic debilitating diseases in the tropics. A hallmark of filariasis is the marked down‐regulation and polarization of host immune responses, yet molecular constituents of parasites causing this state have remained undefined. We describe a 17‐kDa antigen (Av17) of the rodent filarial parasite Acanthocheilonema viteae, which shows amino acid homologies to cystatin C, a major cysteine protease inhibitor belonging to family 2 of the cystatin superfamily. Av17 is released by filariae in vitro. Exported molecules of A. viteae worms are shown to markedly suppress mitogen‐induced T cell proliferation of mice and jirds. Av17 accounts for 45.5% of this suppressive activity in the murine system. Recombinant Av17 (rAv17), expressed in Escherichia coli, exhibits biological activity as a cysteine protease inhibitor and was used to examine the immunomodulatory effects. rAv17 induces down‐regulation of murine T cell responses to mitogens, to T cell receptor cross‐linking by anti‐CD3 antibodies and to specific antigens, and at the same time up‐regulation of interleukin‐10. Hence, this filarial cystatin is a likely effector molecule of immunomodulation and a potential target for antifilarial intervention.
Evidence for a CD4‐associated calcium influx independent of the phosphoinositide transduction pathway in human T cells
Authors: Lafont Virginie , Fischer Thierry , Zumbihl Robert , Faure Sandrine , Hivroz Claire , Rouot Bruno , Favero Jean 
Published: March 2007

AbstractWe recently showed, using human Jurkat T cell variants lacking the T cell receptor (TCR)/CD3 complex, that the lectin jacalin is able to trigger intracellular calcium increase provided that CD4 is expressed on the cell surface. Involvement of the CD4 molecule in jacalin‐induced biological effects was furthermore demonstrated in differentiated U937 myelomonocytic cells expressing or not expressing CD4, and is confirmed here in human CD4‐transfected mouse thymoma cells. In the present paper, we analyze the CD4‐associated calcium response triggered by jacalin independently of the TCR/CD3 complex. We show that the observed calcium rise results from a direct long‐lasting calcium influx from the outside without release of calcium from intracellular stores. We demonstrate that it is independent of the phosphoinositide phospholipase C transduction pathway. Moreover, we show that this peculiar calcium response can be blocked by protein tyrosine kinase inhibitors (herbimycin and genistein) giving evidence of the involvement of a protein tyrosine kinase, the best candidate of which is the CD4‐associated p56lck. Altogether, our results suggest that, independently of the TCR/CD3 complex, CD4 may be involved in the triggering of a calcium signal dependent on a protein tyrosine kinase and independent of the phosphoinositide transduction pathway.
Proteasome regulation of Fas ligand cytotoxicity
Authors: Matsui Ken , Omura Satoshi , Cui Haili , Schauer Stephanie L. , Sonenshein Gail E. , Ju Shyr‐Te 
Published: March 2007

AbstractThe role of NF‐xB in regulating FasL‐mediated cytotoxicity was investigated by using lactacystin. Lactacystin is a microbial metabolite known to inhibit only the protease activity of the proteasome, which is required for NF‐xB translocation. When activated by immobilized anti‐CD3 monoclonal antibody, hybridoma T cells (5D5) degraded IxBβ, translocated NF‐xB into the nucleus, transcribed immediate‐early genes and the Fas ligand (FasL) gene, and expressed FasL‐mediated cytotoxicity. Lactacystin strongly blocked IxBβ degradation and the translocation of NF‐xB (p50/RelA heterodimer), but had little effect on the expression of the transcription factors, Oct‐1 and AP‐1. Moreover, lactacystin did not inhibit the nuclear translocation of NF‐ATp whereas cyclosporin A inhibited the translocation of both NF‐xB and NF‐ATp. The expression of c‐myc and nur77, two immediate‐early genes implicated in FasL gene activation, was blocked by lactacystin. Subsequently, the expression of FasL gene and FasL‐mediated cytotoxicity was inhibited. LLnL, a well‐known peptide aldehyde which inhibits the protease activities of the proteasome and cysteine proteases, also inhibited NF‐xB translocation and FasL‐mediated cytotoxicity. However, these events were not inhibited by the highly specific cysteine protease inhibitor E64. These observations provide further evidence that FasL cytotoxicity is regulated by the proteasome. Furthermore, lactacystin must be added early in order to efficiently inhibit the induction of FasL cytotoxicity, indicating that the early events are critical for FasL gene activation. Our study integrates the proteasome‐dependent IxB degradation and NF‐xB translocation into a T cell activation cascade which results in FasL gene activation and the expression of FasL‐mediated cytotoxicity.
Mouse CD23 regulates monocyte activation through an interaction with the adhesion molecule CD11b/CD18
Authors: Lecoanet‐Henchoz Sybille , Plater‐Zyberk Christine , Graber Pierre , Gretener Denise , Aubry Jean‐Pierre , Conrad Daniel H. , Bonnefoy Jean‐Yves 
Published: March 2007

AbstractCD23 is expressed on a variety of hemopoietic cells. Recently, we have reported that blocking CD23 interactions in a murine model of arthritis resulted in a marked improvement of disease severity. Here, we demonstrate that CD11b, the α chain of the β2 integrin adhesion molecule complex CD11b/CD18 expressed on monocytes interacts with CD23. Using a recombinant fusion protein (ZZ‐CD23), murine CD23 was shown to bind to peritoneal macrophages and peripheral blood cells isolated from mice as well as the murine macrophage cell line, RAW. The interactions between mouse ZZ‐CD23 and CD11b/CD 18‐expressing cells were significantly inhibited by anti‐CD11b monoclonal antibodies. A functional consequence was then demonstrated by inducing an up‐regulation of interleukin‐6 (IL‐6) production following ZZ‐CD23 incubation with monocytes. The addition of Fab fragments generated from the monoclonal antibody CD11b impaired this cytokine production by 50%. Interestingly, a positive autocrine loop was identified as IL‐6 was shown to increase CD23 binding to macrophages. These results demonstrate that similar to findings using human cells, murine CD23 binds to the surface adhesion molecule, CD11b, and these interactions regulate biological activites of murine myeloid cells.
Human mast cells express functional TrkA and are a source of nerve growth factor
Authors: Nilsson Gunnar , Forsberg‐Nilsson Karin , Xiang Zou , Hallböök Finn , Nilsson Kenneth , Metcalfe Dean D. 
Published: March 2007

AbstractMast cells are the principal effector cells in IgE‐dependent hypersensitivity reactions. Despite reports that rodent mast cells proliferate in the presence of nerve growth factor (NGF), human mast cells reportedly do not respond to this factor. To determine if human mast cells express the NGF receptors, TrkA tyrosine receptor and the low affinity NGF receptor (LNGFR), we first analyzed the mRNA expression by RT‐PCR of TrkA and LNGFR in a human mast cell line (HMC‐1) and in human mast cells cultured in the presence of stem cell factor. Both HMC‐1 and cultured human mast cells were found to express TrkA but not LNGFR. TrkA protein was demonstrated by Western blot analysis of HMC‐1 lysates. Using flow cytometric analysis and mast cell tryptase as a mast cell marker, both HMC‐1 cells and cultured human mast cells were shown to co‐express tryptase and TrkA. Treatment of mast cells with NGF resulted in phosphorylation of TrkA on tyrosine residues as detected by immunoblotting with an antiphosphotyrosine antibody. Furthermore, NGF induced the immediate early gene c‐fos in HMC‐1 cells. HMC‐1 cells and cultured human mast cells were also found to express NGF mRNA, and conditioned medium from HMC‐1 cells stimulated neurite outgrowth from chicken embryonic sensory ganglia in culture. This effect was blocked by anti‐NGF. Thus, mast cells express functional TrkA and synthesize NGF, suggesting a mechanism by which NGF may act as an autocrine factor for human mast cells, and by which mast cells and nerves may interact.
Antagonism of cytotoxic T lymphocyte‐mediated lysis by natural HIV‐1 altered peptide ligands requires simultaneous presentation of agonist and antagonist peptides
Authors: Sewell Andrew K. , Harcourt Gillian C. , Goulder Philip J. R. , Price David A. , Phillips Rodney E. 
Published: March 2007

AbstractMutations in human immunodeficiency virus (HIV) cluster in cytotoxic T lymphocyte (CTL) epitopes (Phillips, R. E. et al., Nature 1991. 354: 453) and are subject to immune‐mediated positive selection (Price, D. A. et al., Proc. Natl. Acad. Sci. USA 1997. 94: 1890). We studied the effects of naturally occurring mutations in the HIV‐1 p17 Gag HLA A2 restricted epitope SLYNTVATL on recognition by anti‐HIV CTL. Most of these naturally occurring mutants escaped killing by one CTL line and the majority acted as CTL antagonists. We also investigated whether CTL exposed to a strict antagonist peptide restricted by HLA A2 were unresponsive when exposed to targets presenting the wild‐type sequence. The results show that antagonism of anti‐HIV CTL killing requires the simultaneous presence of agonist and antagonist peptide. We found no evidence that CTL exposed to an antagonist received a functionally negative signal since these CTL retained an unimpaired capacity to lyse targets bearing wild‐type peptide.
CpG‐containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen: A new class of vaccine adjuvants
Authors: Lipford Grayson B. , Bauer Marc , Blank Christian , Reiter Rudi , Wagner Hermann , Heeg Klaus 
Published: March 2007

AbstractForeign DNA has been shown to impinge on immune cell function by an as yet unidentified mechanism. We and others have demonstrated that single‐stranded (ss) DNA containing the motif CpG flanked by two 5′ purines and two 3′ pyrimidines are mitogenic for B cells and activate macrophages to release tumor necrosis factor‐α, interferon‐γ, interleukin (IL)‐6 or IL‐12. Because of these proinflammatory responses we investigated if ssDNA would serve as a potential vaccine adjuvant. Here we show that CpG‐containing oligonucleotides represent a powerful adjuvant for both humoral and cellular immune responses. When ssDNA was incorporated into inocula, specific antibody titers of the IgG2 isotype were enhanced by greater than 100‐fold. Primary cytotoxic T lymphocyte responses generated to either unprocessed protein antigen or major histocompatibility complex class I‐restricted peptide were exceedingly strong. Evidence is also provided that oligomers directly influenced T cell receptor‐triggered T cell proliferation. Thus ssDNA oligomers may serve as inexpensive and safe vaccine adjuvants and, in addition, differential effects due to sequence may allow for directed responses.
An Fcγ receptor I (CD64)‐negative subpopulation of human peripheral blood monocytes is resistant to killing by antigen‐activated CD4‐positive cytotoxic T cells
Authors: Grage‐Griebenow Evelin , Baran Jaroslaw , Loppnow Harald , Los Marek , Ernst Martin , Flad Hans‐Dieter , Pryjma Juliusz 
Published: March 2007

AbstractIt has been demonstrated that in monocyte/T cell co‐cultures activated with recall antigens, cytotoxic T cells were generated which are able to reduce the number of antigen‐presenting monocytes. In previous studies we could show that a minor subset of monocytes, the Fcγ receptor I‐negative (CD64−) monocytes, exhibits significantly higher antigen‐presenting capacity than the main population of monocytes (< 90%) which are Fcγ receptor I‐positive (CD64+). Therefore, we addressed the question whether they are also differentially susceptible to T cell‐mediated killing. In the present study we demonstrate that the CD64− monocyte subset is more resistant to killing by antigen‐activated T cells than CD64+ monocytes, as indicated by a higher viability and recovery of CD64− monocytes. This mechanism involves CD95 (Fas) antigen, since monocyte death in co‐cultures with antigen‐activated T cells could be partially reduced by blocking anti‐Fas monoclonal antibodies (mAb). In agreement with this finding, although CD95 antigen was expressed on CD64+ and CD64− monocytes at comparable levels, killing of CD64− monocytes by activating anti‐Fas mAb was lower than of CD64+ monocytes.