bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific molecular interaction between the insulin receptor and a D product of MHC class I.
Authors: Verland S , Simonsen M , Gammeltoft S , Allen H , Flavell R A , Olsson L 
Published: December 2022

Abstract
The density of MHC class I was determined on a murine thymoma cell line (R1), an H-2 negative variant (R1E), and R1E-derived cell lines in which H-2 expression was restored by transfection of various MHC class I genes (Db, Kb, and truncated Db) and/or a beta-2-microglobulin gene (beta 2-m; B2). Appreciable MHC class I expression was found on R1 cells and on the variants in which MHC class I expression was restored by transfection of Db/beta 2-m or Kb/beta 2-m genes. Only approximately 20% difference was observed between the number of Db molecules and Kb molecules on the R1E/B2/Db and on R1E/B2/Kb, respectively. However, specific insulin binding was significantly different between these lines. By using a computer assisted curve fitting program, the insulin binding data for R1 and R1E/B2/Db cell lines best fitted a two-site model (K approximately 6 x 10(-9) M for high-affinity sites and a 2 to 3 x 10(-7) M for low-affinity sites), whereas all other lines only expressed one type of insulin binding site. These sites were unrelated to IGF-I and IGF-II receptors. Cross-linking of 125I-labeled insulin demonstrated specific binding of the ligand to a Mr approximately 130,000 dalton band in all lines. In the R1E/B2/Db cells, insulin also cross-linked to cell membrane molecules with Mr approximately 48,000 and approximately 60,000 Da, which were identified by immunoprecipitation to be the H chain of MHC class I and the heavy chain of MHC class I plus beta 2-m, respectively. It is concluded that the insulin receptors in the cell membrane interact specifically with D-products of MHC class I and that class I molecules of MHC may have a crucial role in insulin receptor expression. This may reflect a more general nonimmunologic role of MHC class I.
Eosinophil cationic protein cDNA. Comparison with other toxic cationic proteins and ribonucleases.
Authors: Barker R L , Loegering D A , Ten R M , Hamann K J , Pease L R , Gleich G J 
Published: December 2022

Abstract
Human eosinophil granules contain several basic proteins including eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) and major basic protein (MBP). ECP and MBP are potent helminthotoxins while EDN is less so. Both ECP and EDN possess neurotoxic and ribonuclease activities. A clone representing ECP mRNA was isolated from an eosinophil lambda ZAP cDNA library. The cDNA sequence codes for a preprotein of 160 amino acids and a protein of 133 amino acids, the amino terminus of which is identical to the known partial amino acid sequence of ECP. The ECP nucleotide sequence shows similarity to EDN, rat pancreatic ribonuclease, and human angiogenin; all are members of the ribonuclease gene superfamily. Although the deduced amino acid sequence of ECP shares identical active site and substrate binding site residues with EDN, angiogenin, and human pancreatic ribonuclease, the ribonuclease activity of ECP is 50 to 100 times less than that of EDN possibly because of the lack of a positively charged residue at human pancreatic ribonuclease position 122. The calculated isoelectric point (10.8), electronic charge (14.5), and cationic charge distribution of ECP are different from those of EDN but similar to those of MBP, which may account in part for the greater helminthotoxic activity of ECP when compared to EDN. These data suggest that ECP and EDN are derived from a common ancestral ribonuclease gene and that ECP has evolved into a potent helminthotoxin similar in some respects to MBP, while losing much of its ribonuclease activity.
Plasminogen activator and prostaglandin E2 levels in human synovial fibroblasts. Differential stimulation by synovial activator and other cytokines.
Authors: Leizer T , Hamilton J A 
Published: December 2022

Abstract
Interaction between cells of the immune system and of the synovial tissue may be contributing to the pathogenesis of rheumatoid arthritis. Cytokines, produced by PBMC, were tested for their effects on plasminogen activator activity and PGE2 levels of a number of human synovial fibroblast-like cell lines. Evidence was obtained for a human monocyte polypeptide, synovial activator, which can stimulate synovial cell plasminogen activator activity but not PGE2 levels. Purified human rIL-1 alpha and IL-1 beta increased the levels of both products in the supernatants of the synovial cells; TNF-alpha raised the PGE2 levels but raised the plasminogen activator activity only weakly and inconsistently. Synovial activator was further distinguished from IL-1 alpha and IL-1 beta (and TNF-alpha) on biochemical, immunologic, and functional criteria. No other purified native or recombinant human cytokine tested was active on the synovial cells when judged by the criteria in question. Synovial activator could therefore be a novel monokine. The differences in the type of response elicited by the various cytokines in the synovial fibroblast-like cells could have implications for the understanding of the cellular interactions occurring in rheumatoid lesions.
Characteristics of protective immunity in mice induced by drug-attenuated larvae of Schistosoma mansoni. Antigen localization and antibody responses.
Authors: Mountford A P , Coulson P S , Saunders N , Wilson R A 
Published: December 2022

Abstract
Partial resistance to reinfection developed in mice with immature infections of Schistosoma mansoni treated with the drug Ro11-3128, whereas mice vaccinated with irradiated cercariae and treated in a similar way did not become immune. Persistence of drug-treated parasites in the skin and draining lymph nodes, which prolonged the opportunity for efficient Ag presentation, was necessary for the development of protective immunity. Death and clearance of parasites solely in the skin, was not sufficient to induce protection. The expansion in the number of lymphocytes in the skin-draining nodes after vaccination, was reflected in the contrasting levels of resistance induced by the different drug-treatment regimes. Challenge parasites were eliminated predominantly after they reached the lungs. An investigation of antibody reactivity revealed an immunodominant response against a doublet of Ag of Mr 97 to 99 kDa. Recognition of this complex by antisera from different groups of mice was not related to their immune status. Western blots and inhibition analysis showed that this doublet has epitopes in common with the Sm97/paramyosin protective Ag, originally identified by antisera reactivity from mice immunized with a nonliving vaccine.
Dual action of anti-sporozoite antibodies in vitro.
Authors: Nudelman S , Rénia L , Charoenvit Y , Yuan L , Miltgen F , Beaudoin R L , Mazier D 
Published: December 2022

Abstract
With the use of a double staining technique that permits localization of the sporozoite during the process of entering a host cell, we studied the biologic effects of three mAb directed against determinants contained in the circumsporozoite of Plasmodium yoelii. These mAb, which included one IgM and two IgG3, were studied in primary cultures of rodent hepatocytes inoculated with sporozoites of P. yoelii. These results confirm previous reports of the extended action of antibodies on Plasmodium falciparum after entering hepatocytes by producing a strong intrahepatocyte inhibitory effect in addition to the inhibitory effect on sporozoite entry. As with P. falciparum the intracellular effects on P. yoelii liver stages are only observed when the antibodies are present at the time the sporozoite enters the cell. While carrying out experiments on this phenomenon, it was discovered that, at lowered antibody concentrations, an increase in number of maturing liver schizonts occurs, with the increase or enhancement of infection reaching up to 150% of that of controls. It was also observed that there was an inverse relationship between the antibody concentration that was inhibitory and that which enhanced parasite infectivity.
T cell activation via Leu-23 (CD69).
Authors: Testi R , Phillips J H , Lanier L L 
Published: December 2022

Abstract
The CD69 (Leu-23) activation Ag is a phosphorylated 28 to 32-kDa disulfide-linked homodimer that is rapidly induced after lymphocyte activation. CD69 is not present on the surface of peripheral blood resting T cells, but is constitutively expressed by CD3bright thymocytes. Activation of protein kinase C (PKC) by stimulation of the TCR/CD3 or by phorbol esters directly induces CD69 expression on T cells. In the attempt to elucidate the function of CD69 we investigated the ability of the CD69 glycoprotein to transmit an activation signal. Cross-linking of CD69 by mAb induced a prolonged elevation of intracellular [Ca2+], mostly due to an influx of extracellular Ca2+. This signal alone was unable to effectively activate PKC. When PKC was simultaneously activated by PMA, stimulation of CD69 induced IL-2 and IFN-gamma gene expression, enhancement of CD25 expression, and ultimately IL-2-dependent T cell proliferation. Both CD4+ and CD8+ peripheral T cells responded to CD69-mediated activation. Stimulation of CD69 induced proliferation of thymocytes as well as peripheral T cells, but both required independent PKC activation by PMA. Cyclosporin A, which does not prevent PKC-induced CD69 expression, completely suppressed CD69-induced IL-2 and IFN-gamma gene expression. Although the signal delivered by the CD69 initiates T cell proliferation, it is unable to trigger cytotoxicity programs in CD69+-activated T cells or T cell clones.
Two distinct affinity binding sites for IL-1 on human cell lines.
Authors: Bensimon C , Wakasugi N , Tagaya Y , Takakura K , Yodoi J , Tursz T , Wakasugi H 
Published: December 2022

Abstract
We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated.
Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2.
Authors: Heidenreich S , Gong J H , Schmidt A , Nain M , Gemsa D 
Published: December 2022

Abstract
The macrophage-activating properties of murine recombinant granulocyte-macrophage (GM)-CSF were studied in murine peritoneal macrophages with respect to metabolism, endocytosis, PGE2 and TNF-alpha release, and tumor cytotoxicity. GM-CSF was found to be a potent stimulus for RNA and protein synthesis, glucose consumption, pinocytosis, and FcR-independent phagocytosis. Macrophages were activated by GM-CSF to kill TNF-alpha-insensitive Eb lymphoma cells but failed to generate cytotoxicity against TNF-alpha-sensitive L929 cells. Although GM-CSF alone was incapable of stimulating TNF-alpha release, it primed macrophages for elevated TNF-alpha production in response to IFN-gamma plus LPS. The priming effect of GM-CSF disappeared upon longer incubation (greater than 12 h) and was followed by a strongly reduced responsiveness to stimuli that release TNF-alpha. Late-stage suppression could be reverted by treatment with the cyclooxygenase blocker indomethacin, and GM-CSF-induced priming for enhanced TNF-alpha release was entirely restored. The responsible arachidonic acid product mediating suppression was found to be PGE2, because 1) GM-CSF-primed macrophages released enhanced amounts of PGE2 and 2) indomethacin-restored macrophages were again suppressed when exogenous PGE2 was added back in amounts produced by GM-CSF-primed macrophages. Although GM-CSF potently induced TNF-alpha gene transcription by 20 h of treatment, PGE2 interfered with translation into the secreted TNF-alpha protein. These data show that GM-CSF is capable of priming for the enhanced release of two factors, initially for TNF-alpha and subsequently for PGE2. The temporally delayed generation of these two mediators suggests an autoregulatory circuit in which the later produced PGE2 limits GM-CSF-induced macrophage activation.
Different patterns of inositol polyphosphate production are seen in B lymphocytes after cross-linking of sIg by anti-Ig antibody or by a multivalent anti-Ig antibody dextran conjugate.
Authors: Brunswick M , June C H , Finkelman F D , Mond J J 
Published: December 2022

Abstract
Anti-delta antibody conjugated to 2 x 10(6) m.w. dextran (dex) stimulates B lymphocyte proliferation at 10,000-fold lower concentrations than that required by the unconjugated antibody. Dex conjugated antibody also stimulates a greater and more sustained increase in intracellular ionized calcium [( Ca2+]i) than does the unconjugated anti-Ig antibody. Inasmuch as inositol phosphate metabolites have been linked to rises in [Ca2+]i, we analyzed by FPLC the relative amounts of the inositol polyphosphates (IP) in these cells. Anti-Ig-dextran induced a threefold greater increase in total IP than did the unconjugated anti-Ig. Furthermore, in cells stimulated by unconjugated anti-Ig there was a transient induction of I(1,4,5)P3 followed by a rapid accumulation of the I(1,3,4)P3 isomer with little accumulation of I(1,4)P2, whereas in anti-Ig-dex-stimulated cells there was prolonged elevation of I(1,4,5)P3 with more accumulation of I(1,4)P2. In addition, levels of I(1,3,4,5)P4 were maintained over a longer period of time in B cells stimulated by anti-Ig-dex than in those stimulated by unconjugated anti-Ig. The enhanced ratio of I(1,4,5)P3/I(1,3,4)P3 was also seen when suboptimal concentrations of anti-Ig-dex were used which stimulated a level of total inositol phosphate that was similar to that stimulated by the unconjugated anti-Ig. The possibility that the greater stimulation of increased [Ca2+] by anti-Ig-dex than by unconjugated anti-Ig was a predominant factor in influencing the metabolic pathway of I(1,4,5)P3 was excluded. These results show that 1) stimulation of increases in the various IP isomers occurs in anti-Ig stimulated normal B cells as has been shown in B cell lines and 2) that signal transduction and consequent PIP2 hydrolysis that is stimulated by Ag-mediated cross-linking of sIg is strongly influenced by the extent and type of cross-linking that is induced.
A role for isotype-specific binding factors in the regulation of IgA- and IgG-specific responses by the anti/contrasuppressor T cell circuit.
Authors: Ernst P B , Lee S T , Maeba J , Bienenstock J , Stanisz A M , Paraskevas F 
Published: December 2022

Abstract
Previous studies have shown that the isotype of an antibody response is selected, in part, by the inhibition of isotype-specific suppression. The antisuppressor model predicts that isotype selection is initiated through an interaction between Ag, Ig, and a T cell-derived factor within 6 h of immunization. This report characterizes some of these molecules and their contribution to isotype regulation. Cultures of murine spleen cells stimulated with the T cell-dependent Ag SRBC led to Ag-specific IgG and IgA responses that could be suppressed and then antisuppressed by a molecular complex produced by mixing purified serum Ig with the supernatant of Ag-pulsed macrophages co-cultured with T cells. The supernatants from separate cultures of Ag-pulsed macrophages and rIL-1 alpha stimulated CD4+ T cells, could be pooled and mixed with Ig to produce functional antisuppressive complexes thereby allowing the factors from the different cell types to be studied separately. Adsorption of the co-culture or the rIL-1 alpha stimulated T cell supernatants against monoclonal IgG or IgA, removed IgG and IgA binding factors, respectively, and abrogated the ability to enhance the corresponding isotype. The adherent material could be recovered and used to reconstitute enhancement by the supernatants depleted of the binding factors. When affinity purified IgG or IgA was used as the source of Ig within the antisuppressive complexes, the enhancement of the antibody response was limited to the isotype of the regulatory Ig used to form the complex. Thus, manipulation of the antisuppressive molecules has a predictable effect on isotype selection. Release of isotype-specific binding factors by CD4+ cells by rIL-1 alpha supports the hypothesis that T cell circuits play a role in initiating isotype regulation.
Mapping of epitopes recognized by alloreactive cytotoxic T lymphocytes using inhibition by MHC peptides.
Authors: Heath W R , Vitiello A , Sherman L A 
Published: December 2022

Abstract
To identify epitopes recognized by alloreactive CTL we have examined H-2Kb-specific CTL for their recognition of synthetic peptides with sequences derived from the native Kb class I molecule. Consecutive nested peptides spanning the immunogenic alpha 1 and alpha 2 domains of Kb were tested for their capacity to inhibit CTL clones in their recognition of cells expressing the native Kb molecule. Inhibition by these peptides was found to be an extremely rare event. One peptide (Kb.111-122) did inhibit recognition by one particular CTL clone, clone 13. Upon further investigation it was observed that clone 13 also recognized peptide Kb.111-122 when presented in the context of the syngeneic MHC molecule, Kd. Considering that residues 111 to 122 are located at the base of the antigen groove, and clone 13 is able to recognize Kb.111-122 when presented by syngeneic target cells, we suggest that inhibition of this CTL clone may be due to MHC restricted, self-presentation of peptide rather than to direct binding of free peptide to the TCR. Taken together, these results suggest inhibition of allospecific CTL by MHC peptides is a rare event at least for Kb recognition. Furthermore, they demonstrate the need for caution when interpreting inhibition by peptide as evidence for recognition by the TCR of the corresponding region on the native molecule.
Neonatal injection of CD3 antibody into nonobese diabetic mice reduces the incidence of insulitis and diabetes.
Authors: Hayward A R , Shreiber M 
Published: December 2022

Abstract
Over 80% of nonobese diabetic (NOD) mice develop lymphocytic infiltrates of their pancreatic islets (insulitis) by 6 wk of age and 50% of the females are diabetic by 6 mo of age. The incidence of insulitis in NOD mice injected once as neonates with 250 micrograms of the CD3 antibody, 145.2C11, was 8% at 10 wk of age, increasing to 25% at 32 wk of age. Fewer than 10% of these animals developed diabetes by 8 mo of age. Neonatal administration of 145.2C11 reduced the proliferative responses of spleen cells to mitogen stimulation 2 and 4 wk postinjection and expression of TCR was reduced 1 to 5 wk postinjection. The percentage of CD4 and CD8 cells in the spleen was transiently reduced after injection and the frequency of Pgp-1+-high cells (putative memory cells) was increased 2 to 4 wk postinjection, suggesting that in vivo administration of the antibody caused some T cells to divide as well as transiently reducing T cell numbers. IL-2R expression was not detected on spleen cells in the 4 wk after antibody injection. The phenotypic and functional changes after neonatal CD3 antibody injection resolved by 8 wk of age. The control and injected mice grew normally and made equivalent IgG antibody responses to injected human IgG. Neonatally injected 145.2C11 antibody was cleared from the circulation with a terminal half-life approximating to 21 days but greater than 90% of antigen binding activity was lost 6 days after injection. Protection from diabetes did not follow neonatal elimination of T cells with CD4 and CD8 antibodies, nor the injection of a TCR subset antibody, F23.1. Our data suggest that the neonatal T cell repertoire is open to modulation by a single injection of a CD3 antibody and they offer a new experimental approach to immunotherapy in an animal model of type 1 diabetes.
Alveolar macrophages differ from blood monocytes in human IL-1 beta release. Quantitation by enzyme-linked immunoassay.
Authors: Wewers M D , Herzyk D J 
Published: December 2022

Abstract
Fresh human alveolar macrophages and blood monocytes were stimulated with LPS and assessed for their ability to produce and release antigenic IL-1 beta. Using a sensitive and specific ELISA for IL-1 beta, monocytes released 13.3 +/- 3.1 ng/10(6) cells compared to 3.5 +/- 0.8 ng/10(6) cells for alveolar macrophages (p less than 0.01). To investigate the reason for this difference in IL-1 beta release, monocytes were compared to alveolar macrophages for total IL-1 beta production (i.e., the amount released plus that detected in the lysates). Monocytes produced a total of 19.0 +/- 3.2 ng/10(6) cells whereas alveolar macrophages produced 24.8 +/- 5.6 ng/10(6) cells (p = 0.37). The relative increase in alveolar macrophage intracellular IL-1 beta was confirmed by Western blot analysis of cell lysates. Thus, the limitation in IL-1 release from alveolar macrophages appears to be due to a decrease in the processing and release of the IL-1 beta precursor. In addition, TNF production studies demonstrated that the limitation in IL-1 release was not a generalized defect. In contrast to the IL-1 beta data, when TNF was measured from monocytes and macrophages, monocytes released only 14.6 +/- 3.4 ng/10(6), whereas macrophages released 101 +/- 30 ng/10(6) (p less than 0.02). In this same context, when fresh monocytes were allowed to mature in vitro they took on monokine production characteristics similar to alveolar macrophages. In vitro matured monocytes had a greater than 20-fold decrease in their ability to release IL-1 beta and a 6- to 8-fold increase in their ability to release TNF. Taken together, these studies suggest that IL-1 beta release is limited in mature mononuclear phagocytes as compared to fresh blood monocytes, and furthermore, that IL-1 beta regulation differs significantly from that of TNF-alpha.