bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma lipopolysaccharide (LPS)-binding protein. A key component in macrophage recognition of gram-negative LPS.
Authors: Mathison J C , Tobias P S , Wolfson E , Ulevitch R J 
Published: December 2022

Abstract
LPS-binding protein (LBP) binds with high affinity (Kd approximately equal to 10(-9) M) to lipid A of LPS isolated from rough (R)- or smooth (S)-form Gram-negative bacteria as well as to lipid A partial structures such as precursor IVA. To define the role of LBP in regulating responses to LPS we have examined TNF release in rabbit peritoneal exudate macrophages (M phi) stimulated with LPS or with complete or partial lipid A preparations in the presence or absence of LBP. In the presence of LBP, M phi showed increased sensitivity to S- and R-form LPS as well as synthetic lipid A. Compared with LPS or lipid A, up to 1000-fold greater concentrations of partial lipid A structures were required to induce TNF production. However, consistent with our previous observations that these structures bind to LBP, TNF production was increased in the presence of LBP. In contrast, LBP did not enhance or inhibit TNF production produced by heat-killed Staphylococcus aureus, peptidoglycan isolated from S. aureus cell walls, or PMA. Potentiated M phi responsiveness to LPS was observed with as little as 1 ng LBP/ml. Heat-denatured LBP (which no longer binds LPS), BPI (an homologous LPS-binding protein isolated from neutrophils), or other serum proteins were without effect. LBP-treated M phi also showed a more rapid induction of cytokine mRNA (TNF and IL-1 beta), higher steady-state mRNA levels and increased TNF mRNA stability. These data provide additional evidence that LBP is part of a highly specific recognition system controlling M phi responses to LPS. The effects of LBP are lipid A dependent and importantly, extend to LPS preparations isolated from bacteria of R- and S-form phenotype.
EBV increases phosphoinositide kinase activities in human B cells.
Authors: Suzuki Y , Ohsugi K , Ono Y 
Published: December 2022

Abstract
To determine whether EBV affects phosphoinositide kinase activities of human B cells, we compared the activities between EBV- and EBV+ human B cell lymphoma lines. The two types of human B cells contained both phosphatidylinositol (PtdIns) 4-kinase and phosphatidylinositol 4-phosphate (PtdIns(4)P) kinase activities irrespective of the presence of EBV. However, both activities were increased in EBV+ cells compared to EBV- cells. The increases were associated with neither altered Km values for substrates nor altered elution profiles in DEAE-cellulose chromatography. Furthermore, expression of a latent EBV protein, EBV nuclear Ag1 (EBNA1) in BHK cells by the transfection of EBNA1 DNA was accompanied by increased PtdIns 4-kinase and PtdIns(4)P kinase activities. These increases also were not associated with altered Km values for substrates. However, phospholipase C activity was altered in neither EBV+ cells nor in EBNA1-expressing cells. These results indicate that EBV selectively increases the two phosphoinositide kinase activities in human B cells, although the viral gene product has no intrinsic phosphoinositide kinase activity. PtdIns 4-kinase and PtdIns(4)P kinase cooperatively synthesize PtdIns 4,5-bisphosphate, the major source of 1,2-diacylglycerol and inositol 1,4,5-triphosphate, the two second messengers in transducing signals for cell activation. Such increase therefore may play a role in EBV-induced human B cell activation.
Involvement of somatically acquired ecotropic viruses in the immunogenicity of nude-transplanted NIH/3T3 transformed cell lines.
Authors: Sensi M , Bergomi M , Panceri P , Castelli C , Lupetti R , Traversari C , Carbone G , Parmiani G 
Published: December 2022

Abstract
Immunogenic tumor variants were previously derived after transplantation in vivo into nude mice of NIH/3T3-transformed cell lines. Nude-passaged cell lines were rejected by immunocompetent H-2q NIH mice, were recognized by specific CTL clones, and expressed new retroviral Ag. The aim of the present work was to investigate whether somatically acquired proviral sequences were present in the genome of nude-passaged cells and to test directly for a causative relationship between murine leukemia virus (MuLV) expression and immunogenicity. Southern blot analysis of PstI-digested DNA indicated that in contrast to the parental NIH/3T3 transformed cell lines (pT, T12N/5a, NS-1) all the nude-passaged immunogenic variants (pT-nude, T12N/5a-nude, NS-1-nude) contained newly acquired ecotropic-related proviruses. Immediately after in vitro establishment, these tumors displayed multiple integration sites as assessed by analysis of 3' proviral-cellular junctions. Long term in vitro culture of one of the cell lines (pT-nude) resulted in a cell line (pT-nude/vitro) that was clonal or oligo-clonal with respect to viral integration. Northern blot analysis established that the new proviruses were actively transcribed in all the immunogenic variants. To assess whether the somatically acquired ecotropic proviral sequences encode for target structures recognized by specific CTL, obtained after immunization of NIH mice with pT-nude, the parental cell line pT was transfected with plasmids containing the entire AKV MuLV genome, the cloned AKV gag or env genes. Screening of transfectants for their ability to stimulate the production of TNF by anti-pT-nude effectors indicated that cells transfected with the entire ecotropic virus or with MuLV-env gene products could be recognized by an NIH anti-pT-nude CTL line and NIH anti-pT-nude Kq-restricted CTL clones as well as the immunizing target pT-nude.
Staphylococcal enterotoxin-mediated human T-T cell interactions.
Authors: Koning F , Rust C 
Published: December 2022

Abstract
Staphylococcal enterotoxins (SE) are known to stimulate a large proportion of T cells. SE bind to MHC-class II molecules on APC and a particular segment of certain TCR V beta and V gamma gene products. Resting human T cells do not express HLA class II Ag and therefore cannot present SE to T cells. Activated human T cells, however, do express HLA-DR, -DP, and -DQ Ag and could consequently serve as APC for SE. As such, local immune responses to SE might be regulated and/or abrogated by SE-mediated T-T cell interactions leading to T cell destruction. We have investigated if such SE-mediated T-T cell interactions can occur in vitro using human cytolytic TCR-alpha beta+ and TCR-gamma delta+ T cell clones. We demonstrate that the TCR-alpha beta+ T cell clones can efficiently present staphylococcal enterotoxin A (SEA) to each other: T cell clones coated with SEA are lysed by SEA-reactive T cell clones but not by a SEA-nonreactive T cell clone. Furthermore, the SEA-reactive TCR-alpha beta+ clones (but not the SEA-nonreactive clone) destruct themselves in the presence of SEA at low concentrations of SEA (less than 0.01 microgram/ml). Also, SEA-coated T cell clones can induce proliferative responses although such responses are much weaker than those induced when B cells are used as stimulator cells. In contrast, the SEA-reactive TCR-gamma delta+ T cell clones are resistant to autokilling in the presence of SEA and they do not lyse SEA-coated TCR-gamma delta+ targets. However, such targets can be lysed by TCR-alpha beta+ effector cells. These results indicate that TCR-gamma delta+ cells are relatively resistant to lysis and that during local nonspecific immune responses triggered by SE, which induces HLA-class II expression by the responding T cells, SE-mediated T-T cell interactions may play a role in the regulation and/or abrogation of these immune responses.
Comparison of the T cell receptors on insulin-specific hybridomas from insulin transgenic and nontransgenic mice. Loss of a subpopulation of self-reactive clones.
Authors: Poindexter N J , Landon C , Whiteley P J , Kapp J A 
Published: December 2022

Abstract
Transgenic mice expressing the human insulin gene do not produce insulin-specific antibody after injection of human insulin. Nevertheless, they have some peripheral T cells that proliferate to human insulin in vitro. To investigate the nature of these T cells, human insulin-specific T cell hybridomas were produced from transgenic and nontransgenic mice. Transgenic hybridomas required more insulin to achieve maximum responses and they produced lower levels of lymphokines than nontransgenic hybridomas. The majority of nontransgenic hybridomas recognized only human and pork insulin whereas transgenic hybridomas recognized beef, sheep, and/or horse insulin in addition to human and pork insulin. The TCR expressed by transgenic and nontransgenic hybridomas were determined by Northern analysis. Both types of hybridomas used several different V alpha and V beta gene families and no favored association between V alpha and V beta gene usage was detected in either type. V beta 1 was used by 7 of 16 nontransgenic hybridomas but only by 1 of 16 transgenic hybridomas. V beta 6 receptors were predominantly expressed by the transgenic hybridomas and all V beta 6-bearing hybridomas recognized beef as well as human insulin. The differences in Ag reactivity and TCR gene usage suggest that V beta 1-bearing human insulin-reactive T cells were clonally deleted or inactivated in the transgenic animal. Other clones, representing a minor subpopulation in nontransgenic mice, were recovered from transgenic mice.
IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression.
Authors: Arima N , Kuziel W A , Grdina T A , Greene W C 
Published: December 2022

Abstract
Using electrophoretic mobility shift assays and DNA-protein cross-linking techniques, we demonstrate that IL-2 binding to functional forms of the human IL-2R activates nuclear expression of the eukaryotic transcription factor NF-kappa B. These inductive effects of IL-2 were observed in three different cellular systems including human Jurkat T cells stably transfected with IL-2R beta cDNA, mouse pro-B BA/F3 cells stably expressing human IL-2R beta chains either alone or in combination with human or murine IL-2R alpha chains, and purified primary resting human T cells constitutively displaying small numbers of IL-2R beta molecules. IL-2 activation of nuclear NF-kappa B expression is regulated in part at a post-translational level, involving the rapid translocation of both the 50- and 65-kDa subunits of NF-kappa B from the cytoplasm to the nucleus. However, IL-2 induction also produced an increase in mRNA for NF-kappa B p105, indicating an additional pretranslational component of regulation. In contrast, IL-2 exerts only minor effects on NF-kappa B p65 mRNA expression. IL-2 induction of NF-kappa B through the IL-2R beta subunit was both correlated with activation of the endogenous IL-2R alpha gene and critically dependent upon the presence of a serine-rich cytoplasmic domain within IL-2R beta (amino acid residues 267-312). This domain has previously been shown to be essential for IL-2-induced cell growth and may correspond to a binding site for an IL-2R beta-associated tyrosine kinase. Together, these findings suggest that NF-kappa B may play an important role as one intracellular second messenger relaying signals from the plasma membrane to cell nucleus that leads to IL-2-induced activation and growth.
Regulation of basal tyrosine phosphorylation of the B cell antigen receptor complex by the protein tyrosine phosphatase, CD45.
Authors: Lin J , Brown V K , Justement L B 
Published: December 2022

Abstract
Signal transduction via the B cell AgR complex has recently been shown to be dependent on the activation of one or more protein tyrosine kinases. Similarly, it has been found that signal transduction requires the expression of the protein tyrosine phosphatase CD45. Thus, transduction of a signal after AgR cross-linking must involve the coordinate interaction of these two enzymatic activities. It is therefore logical to hypothesize that the competence of the B cell to respond to ligands that bind the AgR may be dependent on the maintenance of an equilibrium between the tyrosine phosphorylation and dephosphorylation of specific signal transduction components. We have demonstrated in the present study that in resting B cells, the basal level of AgR complex tyrosine phosphorylation is regulated by cellular protein tyrosine phosphatases. Treatment of cells with the protein tyrosine phosphatase inhibitor, Na3VO4, resulted in rapid hyperphosphorylation of the receptor complex. Based on this observation, experiments were designed to examine the role of CD45 in regulation of AgR complex phosphorylation. Treatment of B cells with anti-CD45 mAb alone was found to have no effect on cytoskeletal association of CD45 or on its distribution within the membrane. Addition of a secondary cross-linking reagent, however, induced the association of CD45 with the cytoskeleton and caused capping. Subsequent studies demonstrated that increased tyrosine phosphorylation of the mIg-associated proteins MB-1 and B29 could be induced after incubating cells with anti-CD45 mAb and a secondary cross-linker, but not after the addition of anti-CD45 mAb alone. Changes in tyrosine phosphorylation of MB-1 and B29 were found to correlate with the cytoskeletal association of CD45. Interestingly, although cross-linking CD45 induced alterations in its association with the cytoskeleton and in its distribution within the membrane, no significant change in the level of protein tyrosine phosphatase activity could be detected under these conditions. These findings support the possibility that ligand binding to CD45 can induce biochemical and/or physical alterations in the molecule that presumably inhibit its ability to interact with specific substrates in the cell, thereby shifting the established equilibrium between tyrosine-specific phosphorylation and dephosphorylation.
Molecular cloning of the murine IL-1 beta converting enzyme cDNA.
Authors: Nett M A , Cerretti D P , Berson D R , Seavitt J , Gilbert D J , Jenkins N A , Copeland N G , Black R A , Chaplin D D 
Published: December 2022

Abstract
IL-1 beta is a potent modulator of immune and inflammatory responses. Murine IL-1 beta is initially synthesized as an inactive 33-kDa pro-molecule that is activated by proteolytic cleavage between Asp-117 and Val-118 to generate the 17-kDa mature IL-1 beta protein. This cleavage is catalyzed by a specific protease that has been designated the IL-1 beta converting enzyme (or IL-1 beta convertase). We have used a human IL-1 beta convertase cDNA to isolate murine convertase cDNA from a WEHI-3 library. These cDNA predicted that the murine convertase is a 402-residue protein. Overall, the murine convertase showed 71% nucleotide and 62% predicted amino acid sequence identity with the human convertase. Southern blot analysis of interspecific backcross mice indicated that the murine IL-1 beta convertase is encoded by a single copy gene located on murine chromosome 9. The murine convertase showed broad constitutive expression, being detected in mononuclear phagocyte and T lymphocyte cell lines as well as in spleen, heart, brain, and adrenal glands. The expression of the murine convertase in mononuclear phagocytes was up-regulated by treatment with LPS or rIFN-gamma. These studies establish that the IL-1 beta convertase is an evolutionarily conserved, widely expressed enzyme that can be regulated at a pretranslational level.
Retinoic acids inhibit activation-induced apoptosis in T cell hybridomas and thymocytes.
Authors: Iwata M , Mukai M , Nakai Y , Iseki R 
Published: December 2022

Abstract
Apoptosis is induced in immature thymocytes and T cell hybridomas upon stimulation via the TCR/CD3 complex. This phenomenon appears to be related to negative selection of T cell clones in the thymus. In T cell hybridomas, it has been shown that glucocorticoids inhibit TCR/CD3-mediated apoptosis, whereas glucocorticoids alone induce apoptosis. All-trans-retinoic acid (RA) at 0.1 to 10 microM also inhibited TCR/CD3-mediated apoptosis assessed by DNA fragmentation and cytolysis, but RA alone hardly induced apoptosis. RA enhanced the effects of glucocorticoids to induce apoptosis and to inhibit TCR/CD3-mediated apoptosis. TCR/CD3-mediated stimulation can be mimicked by the combination of ionomycin, a calcium ionophore, and PMA, an activator of protein kinase C, and the combination-induced DNA fragmentation was also inhibited by RA. RA, however, failed to inhibit the combination-induced increase in intracellular Ca2+ concentration or the combination-induced translocation of protein kinase C from the cytosolic fraction to the particulate fraction. Time course studies of RA addition into the culture indicated that a 3- to 6-h delay in the addition of RA did not reduce its inhibitory effect on anti-CD3-induced DNA fragmentation. These results suggest that RA interferes with the apoptotic process at some point after its initiation stage. It has been suggested that negative selection involves not only TCR/CD3-mediated signals but also LFA-1-mediated signals. RA at 0.01 to 1 microM significantly inhibited the induction of thymocyte apoptosis by co-immobilized mAb to CD3 and LFA-1 molecules. RA by itself hardly induced apoptosis, but enhanced glucocorticoid-induced apoptosis. The results suggest that thymic selection might be influenced by RA at near-physiologic concentrations. The receptors of glucocorticoids and RA belong to the erbA oncogene-related steroid hormone receptor superfamily. Thyroid hormones and 1 alpha,25-dihydroxy vitamin D3, whose receptors also belong to the superfamily, failed to modulate apoptosis in both T cell hybridomas and thymocytes.
A novel post-translational incorporation of tyrosine into multiple proteins in activated human neutrophils. Correlation with phagocytosis and activation of the NADPH oxidase-mediated respiratory burst.
Authors: Nath J , Ohno Y , Gallin J I , Wright D G 
Published: December 2022

Abstract
Activation of human neutrophils by PMA causes a post-translational incorporation of 14C-labeled tyrosine into multiple neutrophil (PMN) proteins, that is distinctly different from the enzymatic tyrosinolation of tubulin in FMLP-stimulated PMN. Post-translational incorporation of other radiolabeled amino acids, including the structurally similar amino acid phenylalanine, does not occur under identical conditions of neutrophil activation, suggesting an involvement of the phenolic hydroxyl group of tyrosine in the PMA-mediated reaction. Similar to the stimulation of PMN tubulin tyrosinolation by FMLP, the PMA-induced incorporation of tyrosine into multiple PMN proteins is closely associated with activation of the NADPH oxidase-mediated respiratory burst in stimulated PMN and can be inhibited by a variety of reducing agents, inhibitors of peroxidase-mediated reactions, and intracellular scavengers of oxygen radicals. Moreover, the PMA-induced post-translational incorporation of tyrosine does not occur in PMN from patients with chronic granulomatous disease and is significantly reduced (50%) in PMN of an individual with myeloperoxidase deficiency. A similar stimulus-induced incorporation of tyrosine into multiple PMN proteins is also observed in PMN exposed to various phagocytic stimuli, and the incorporated radioactivity in cells undergoing phagocytosis is substantially enriched (40- to 50-fold) in isolated PMN phagolysosomes. Consistent with this latter observation, HPLC fractionation of stimulated PMN proteins and analysis of the incorporated radioactivity reveal that the 14C label is primarily associated with PMN membrane proteins. Furthermore, this post-translational incorporation of tyrosine, like that associated with PMA stimulation, is associated with production of oxygen radicals and the generation of protein carbonyl derivatives, which are indicative of oxidative protein modifications via mixed function oxidases. Our findings indicate that tyrosine incorporation into membrane proteins of stimulated PMN is functionally relevant to the physiologic host-defense responses of human neutrophils undergoing phagocytosis.
A combined immunodeficiency with oligoclonal CD8+, V beta 3-expressing, cytotoxic T lymphocytes in the peripheral blood.
Authors: Kuijpers K C , van Dongen J J , van der Burg P , Roos M T , Vonk J , de Abreu R , de Korte D , van Noesel C J , Weening R S , van Lier R A 
Published: December 2022

Abstract
The diagnosis severe combined immunodeficiency was made in a male infant at the age of 18 wk. Known causes of severe combined immunodeficiency were excluded. The activity of total 5'-nucleotidase (E.C. 3.1.3.5) in the PBMC was found to be strongly decreased. Analysis of the peripheral blood revealed a lymphocytosis, mainly of CD8+ T cells. These lymphocytes expressed high levels of CD29, CD38, CD45RA, and MHC class II molecules but no CD25, CD26, CD27, or CD28 Ag. The cells proliferated poorly to all T cell stimulants tested and no helper activity for IgM secretion could be induced. In contrast to the poor proliferative responses, high levels of TCR-induced cytolytic activity, without lymphokine-activated killer-cell outgrowth, were induced by CD3 mAb. Analysis of TCR-beta gene rearrangements indicated that two clonal populations constituted the majority of the E-rosette+ peripheral blood fraction. Moreover, the vast majority of the CD8+ cells were found to react with a mAb to V beta 3. Polymerase chain reaction on cDNA from peripheral blood cells with primers that amplify TCR V beta elements showed, in agreement with the fluorescence data, an overrepresentation of V beta 3 but absence of usage of approximately 50% of the other V beta elements. Thus, in a severe combined immunodeficiency patient, CD8+ T cells with limited T cell receptor usage and restricted effector functions were found. The observed alterations in the 5'-nucleotidase levels may be secondary to the outgrowth of this population.