bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation.
Authors: Fierz W , Endler B , Reske K , Wekerle H , Fontana A 
Published: December 2022

Abstract
Ia antigens seem to control immune responses on at least two levels. First, they influence the antigen recognition repertoire of the T cells. Second, their variable expression on certain antigen-presenting cells is a powerful regulatory mechanism for the local immune reaction. This is particularly important in the central nervous system (CNS) in which no Ia antigens are normally expressed. Recent experiments in this context have shown that astrocytes are able to express Ia antigens during interaction with T cells, and that they function as antigen-presenting cells. The Ia-inducing activity is produced by activated T cells, and can be replaced by immune interferon (IFN-gamma). In this study we report on the functional and kinetic relationship between Ia antigen expression on astrocytes and the immune-specific activation of T cells by astrocytes. Normal resting astrocytes were found to be negative for Ia antigens by immunofluorescence and by biochemical criteria. Moreover, they are only able to stimulate T cells after they have been induced to express Ia antigens by a signal from the T cells, which is probably mediated by IFN-gamma. In conclusion, the immune-specific interaction between astrocytes and T lymphocytes is a sensitively controlled system that might be pivotal to the development of immune responses in the brain. Malfunction of the system could be an important factor in the pathogenesis of aberrant immune reactions in the CNS, e.g., in multiple sclerosis.
Ecto-5'-nucleotidase can provide the total purine requirements of mitogen-stimulated human T cells and rapidly dividing human B lymphoblastoid cells.
Authors: Thompson L F 
Published: December 2022

Abstract
The ability of mitogen-stimulated human T cells or rapidly dividing human B lymphoblastoid cells to drive their total purine requirements from inosine 5'-monophosphate, inosine, or hypoxanthine was compared. Inosine 5'-monophosphate first must be converted to inosine by the action of the enzyme ecto-5'-nucleotidase before it can be transported into the cell; inosine and hypoxanthine, however, can be transported directly. Mitogen-stimulated human peripheral blood T cells were treated with aminopterin to inhibit purine synthesis de novo and to make the cells dependent on an exogenous purine source. Thymidine was added as a source of pyrimidines. Under these conditions, 30 microM inosine 5'-monophosphate, inosine, and hypoxanthine showed comparable abilities to support [3H]thymidine incorporation into DNA or [3H]leucine incorporation into protein at rates equal to that of untreated control cultures. Similar results were found when azaserine was used to inhibit purine synthesis de novo, and thus DNA synthesis. In parallel experiments with the rapidly dividing human B lymphoblastoid cell line WI-L2, treatment with aminopterin (plus thymidine) inhibited the growth rate by greater than 95%. The normal growth rate was restored by the addition of 30 microM inosine 5'-monophosphate, inosine, or hypoxanthine to the medium. However, in similar experiments with cell line 1254, a derivative of WI-L2 which lacks detectable ecto-5'-nucleotidase activity, inosine and hypoxanthine (plus thymidine), but not inosine 5'-monophosphate (and thymidine) were able to restore the growth inhibition due to aminopterin. These results show that the catalytic activity of ecto-5'-nucleotidase is sufficient to meet the total purine requirements of mitogen-stimulated human T cells or rapidly dividing human B lymphoblastoid cells, and suggest that this enzyme may be important for purine salvage when rates of purine synthesis de novo are limited and/or an extracellular source of purine nucleotides is available.
Characterization of a human interleukin 1 inhibitor.
Authors: Liao Z , Haimovitz A , Chen Y , Chan J , Rosenstreich D L 
Published: December 2022

Abstract
Human urine contains a specific inhibitor of interleukin 1 (IL 1) that is found in increased amounts during fever. This inhibitor was purified by using a sequence of ammonium sulfate fractionation, DEAE cellulose ion-exchange chromatography, molecular sieve chromatography on Sephacryl S-200, affinity chromatography on concanavalin A (Con A) Sepharose, and polyacrylamide gel electrophoresis. Two peaks of IL 1 inhibitory material were eluted from the polyacrylamide gels. One peak contained three proteins of 29, 32, and 67 kd, respectively, which could be visualized by silver staining. The second peak contained only a small amount of the 67 kd protein. A partially purified inhibitor fraction was found to cross-react with antisera directed against two low m.w. urine trypsin inhibitors that are cleavage products of the serum inter-alpha-trypsin inhibitor. Although these findings suggest that the urine IL 1 inhibitor may be related to the inter-alpha-trypsin inhibitor, a more exact identification will require either a homogeneous inhibitor preparation or a monospecific antiserum.
Induction of human T lymphocyte motility by interleukin 2.
Authors: Kornfeld H , Berman J S , Beer D J , Center D M 
Published: December 2022

Abstract
Interleukin 2 (IL 2) is known to have multiple immunoenhancing activities that are related to its ability to promote the proliferation and the expression of effector functions of human T lymphocytes. We investigated the potential of IL 2 to induce human T lymphocyte migration. Unstimulated T cells did not respond to IL 2, but T cells exposed to dextran or phytohemagglutinin did respond to IL 2 concentrations from 0.01 to 10.0 U/ml, with significantly increased migration. This activity could be specifically blocked with anti-Tac antibody. Analysis of T lymphocyte subsets revealed that OKT4+ but not OKT8+ lymphocytes responded to IL 2 in the chemotaxis assay. Checkerboard analysis demonstrated that the IL 2-induced chemoattractant activity was predominantly chemotactic rather than chemokinetic in nature. The activity of IL 2 was compared with that of another chemoattractant lymphokine, lymphocyte chemoattractant factor, which was found to stimulate lymphocyte migration without prior exposure to mitogen, and which was not inhibited by anti-Tac. Our data suggest that the lymphocyte migratory response to IL 2 is under the control of the inducible receptor recognized by anti-Tac in a manner similar to the proliferative response to IL 2, but differs from proliferation in its OKT4+ cell specificity.
Augmentation of mouse natural killer cell activity by LS 2616, a new immunomodulator.
Authors: Kalland T , Alm G , Stålhandshe T 
Published: December 2022

Abstract
The quinoline-3-carboxamide LS 2616 administered to mice in drinking water increased spontaneous cytotoxicity against YAC-1 cells in a dose-dependent manner. The enhancement of spontaneous cytotoxicity was found to be mediated by NK cells, as judged by their lack of adherence to nylon wool columns, relative resistance to treatment with antibodies to Thy-1.2 and complement, and almost total abrogation after depletion of asialo-GM1+ cells. Enhancement of NK activity was evident after 2 days of treatment, was maximal after 4 days, and remained elevated during the 14-day exposure period studied. NK activity returned to control levels 4 days after cessation of treatment. NK activity was significantly increased in spleen, peripheral blood, lymph nodes, and bone marrow of LS 2616-treated mice, while activity in peritoneal exudate cells and thymus remained low. LS 2616 was able to elevate NK activity in several mouse strains studied, including mice homozygous for the beige gene. Serum interferon levels were not increased during treatment with LS 2616. Combined injection of the interferon inducer Poly I:C and LS 2616 did not increase NK activity above that of animals injected with Poly I:C alone. However, Poly I:C, in contrast to LS 2616, increased NK activity in peritoneal exudate cells. Studies at the single cell level revealed that LS 2616 increased NK activity by increasing the number of lytically active cells via recruitment of new target-binding cells and not by increasing the lytic activity of pre-existing binders.
Preparation and characterization of murine monoclonal antibodies that express both cold agglutinin and cryoglobulin activities.
Authors: Patel R D , Brown J C 
Published: December 2022

Abstract
To obtain murine cold agglutinin (CA) and cryoglobulin antibodies, BALB/c mice were hyperimmunized with heat-killed type XIV Streptococcus pneumoniae. The spleen cells of these mice were fused with either the P3 NS1/Ag4. 1 or P3 X63/Ag.653 cell line. Several stable hybridomas were obtained that produced monoclonal antibodies (Mab) that reacted with rabbit and human erythrocytes only at temperatures below 37 degrees C. Three of these Mab were also cryoglobulins, as evidenced by their insolubility at reduced temperature. All of the antibodies studied were IgM(k) and reacted with purified type XIV S. pneumoniae polysaccharide at room temperature. With one exception, all antibodies were specific for N-acetyl-lactosamine, the immunodominant sugar residue expressed on type XIV polysaccharide. Inhibition experiments demonstrated that both CA activity and cryoprecipitation were inhibited by the same sugar compounds in the same order of efficiency. The data presented strongly suggest these CA antibodies are cross-reactive members of a S. pneumoniae-specific population. Cryoprecipitation persisted in antibodies purified under conditions that would exclude the presence of trapped serum antigens. It is therefore proposed that the cryoprecipitation observed is a result of the interactions of the antibody combining sites with carbohydrate residues of adjacent antibody molecules.
Modulation of the biologic activities of IgE-binding factors. VII. Biochemical mechanisms by which glycosylation-enhancing factor activates phospholipase in lymphocytes.
Authors: Akasaki M , Iwata M , Ishizaka K 
Published: December 2022

Abstract
Cells of the T cell hybridoma 23A4 produce IgE-binding factors lacking N-linked oligosaccharides (unglycosylated form) when they are incubated with IgE alone. In the presence of glycosylation-enhancing factor (GEF) or bradykinin, however, the same cells produce IgE-binding factors with N-linked oligosaccharides (glycosylated form). Switching the cells from the formation of unglycosylated IgE-binding factors to the formation of glycosylated factors was accompanied by the release of both glycosylation-inhibiting factor (GIF) in its phosphorylated form, i.e., phosphorylated lipomodulin, and arachidonate from the cells. Analysis of the biochemical processes for the release of GIF from 23A4 cells showed that affinity-purified GEF or bradykinin induced transient phospholipid methylation and diacylglycerol (DAG) formation, and enhanced 45Ca uptake into the cells. Inhibitors of methyltransferases, i.e., 3-deaza-adenosine plus L-homocysteine thiolactone, inhibited not only phospholipid methylation but also DAG formation and GIF release. Exogenously added 1-oleoyl-2-acetyl glycerol, i.e., a DAG that is permeable to the plasma membrane, induced the release of GIF from the cells. It was also found that 12-O-tetradecanoyl-phorbol 13-acetate (TPA) switched 23A4 cells and normal lymphocytes to the selective formation of N-glycosylated IgE-binding factor, and induced the release of GIF from the cells. 32PO4-labeled lipomodulin was detected in the extract of 23A4 cells 3 to 5 min after the addition of GEF, bradykinin, or TPA. These results indicate that GEF and bradykinin induced the activation of methyltransferases and phospholipase C for the formation of DAG, which in turn activated Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) for the phosphorylation of lipomodulin. Because lipomodulin loses phospholipase inhibitory activity after phosphorylation, increased phospholipase A2 activity would be expressed by this process.
Cyclic AMP-dependent protein kinase in Molt 4b lymphoblasts: identification by photoaffinity labeling and activation in intact cells by vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI).
Authors: O'Dorisio M S , Wood C L , Wenger G D , Vassalo L M 
Published: December 2022

Abstract
Molt 4b lymphoblasts have previously been shown to possess a single class of pharmacologically specific, high affinity receptors for vasoactive intestinal polypeptide (VIP). This study further explores the molecular basis for modulation of human lymphocyte function by VIP. Dose-dependent stimulation of adenylate cyclase was observed in Molt lymphoblasts over the range of 0.1 nM to 1 microM VIP. VIP-mediated by guanine nucleotide. Accumulation of intracellular cAMP was observed in the presence of either VIP or the diterpene, forskolin. The effects of these two agonists were synergistic. Two neuropeptides that share sequence homology with VIP were also studied; both peptide histidine isoleucine (PHI) and human pancreatic growth hormone releasing factor (1-44 GHRF) competed for 125I-VIP binding to Molt cells. PHI stimulated intracellular cAMP accumulation and demonstrated synergism with forskolin, whereas GHRF had no effect on cAMP. Photoaffinity labeling of 100,000 X G soluble proteins with 8-N3-[32P]cAMP followed by SDS gel electrophoresis demonstrated the presence of cAMP-dependent protein kinases I and II. Cyclic AMP-dependent protein kinase II predominated in the soluble fraction and was the only isozyme observed in particulate fractions. Protein phosphorylation was studied in Molt 4b cells preincubated with [32P]PO43- followed by addition of media alone, 1 microM peptide, or 10 microM forskolin. Cells were lysed and subjected to two-dimensional electrophoresis. Increased phosphorylation of a specific 41,000 Mr protein was observed after addition of forskolin, VIP, or PHI. A much lower concentration of VIP (1 nM) also caused a significant net increase in phosphorylation, which was of a lower magnitude. In contrast, no net effect on protein phosphorylation was seen with GHRF. These data demonstrate the presence of a functional VIP receptor that is linked to the G protein-adenylate cyclase complex. The demonstration of cAMP-dependent protein kinase and of VIP- and PHI-mediated protein phosphorylation in Molt 4b lymphoblasts provides evidence on a molecular level for neuropeptide modulation of human lymphocyte function.
Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo.
Authors: Pestel J , Dissous C , Dessaint J P , Louis J , Engers H , Capron A 
Published: December 2022

Abstract
In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell clones here studied were restimulated either with IPSm or with schistosomulum Ag, it appears that such IPSm-specific T cell clones could be involved in the concomitant immunity mechanisms.
Construction of novel class I histocompatibility antigens by interspecies exon shuffling.
Authors: Engelhard V H , Yannelli J R , Evans G A , Walk S F , Holterman M J 
Published: December 2022

Abstract
Human and mouse class I histocompatibility antigens share considerable structural homology at both the protein and DNA sequence level. This homology has allowed the production of hybrid class I molecules by the reciprocal exchange of DNA sequences corresponding to equivalent domains of HLA-B7 and either H-2Ld or H-2Dd. It is shown that these genes give rise to protein products that are stably expressed on the surface of murine L cells after DNA-mediated gene transfer. These proteins express only those monoclonal antibody-defined H-2 determinants that are expected based on their genetic construction. The molecules have allowed the localization of a number of polymorphic and monomorphic HLA-specific epitopes. In all but one case, expression of an epitope on a domain does not appear to be influenced by the replacement of adjacent human domains with their murine equivalents, suggesting a considerable degree of structural independence of the domains. Cells expressing the hybrid molecules have also been tested as targets for a panel of HLA-B7-specific cytotoxic T cell clones. The results show that the polymorphic determinants recognized by these clones map to the alpha 1 and alpha 2 domains of the HLA-B7 molecule. No evidence for an influence of species-related amino acid sequence differences in the third extracellular domain on T cell recognition was seen. The results are discussed in light of the proposed domain structure of the class I proteins and the potential use of such molecules for further functional studies.
Immunologic mechanisms in the pathogenesis of virus-induced leukemia. IV. Mechanism of target cell recognition by autoreactive thymocytes.
Authors: Proffitt M R , Kozak C , de la Motte C , Caulfield M J 
Published: December 2022

Abstract
Neonatal infection of mice with Moloney murine leukemia virus (MuLV-M) results in the establishment of a chronic virus-carrier state. Such MuLV-carrier mice exhibit several immunologic abnormalities including generalized immunosuppression and autoimmunity. Previously, we found thymocytes from MuLV-M-carrier mice to be cytotoxic for normal syngeneic and allogeneic fibroblasts but not for xenogeneic (hamster) target cells. However, when the same syngeneic or allogeneic target cells were infected with MuLV-M, they were "spared" from the autoreactivity, leading us to speculate that the MuLV receptor on the target cell membrane was involved in the autoreactivity. To address this question, we tested MuLV-carrier thymocytes for their ability to lyse hamster/mouse-hybrid target cells; some of which possessed chromosome 5 (which codes for the ecotropic MuLV receptor). Of the nine hybrid cell lines initially tested, only the five clones that carried chromosome 5 were killed by the autoreactive thymocytes. In additional experiments, we noted that the cytotoxic reaction was inhibited in the presence of a monoclonal antibody that reacts with an MuLV-M gp70 epitope. The results suggest that the autoreactive cytotoxicity is mediated, at least in part, through the formation of a "bridge" between MuLV budding from the membrane of the thymocytes and the ecotropic MuLV receptor on the target cells.
Systematic comparison of antibody-mediated mechanisms of keratinocyte lysis in vitro.
Authors: Norris D A , Ryan S B , Kissinger R M , Fritz K A , Boyce S T 
Published: December 2022

Abstract
We have conducted a systematic comparison of lysis of TNP-coated keratinocyte targets by TNP-specific antibody, by antibody plus complement, by antibody-dependent cellular cytotoxicity (ADCC), and by natural killing with the use of monocyte, lymphocyte, and neutrophil effectors. With chromium-release assays, human keratinocytes, HEp-2 cells (transformed human keratinocytes), PAM 212 cells (transformed mouse keratinocytes), and RSC (transformed rabbit keratinocytes) were all susceptible to monocyte- and lymphocyte-mediated ADCC (p less than 0.01 to p less than 0.02). All trypsinized keratinocyte targets were also susceptible to natural killing by monocyte or lymphocyte effectors (p = 0.05 to p less than 0.001). Antibody and antibody plus complement were poor mediators of keratinocyte lysis. If protein and complex lipid synthesis of keratinocytes were inhibited by 16-hr cycloheximide preincubation, then keratinocytes were susceptible to complement-mediated lysis, implying that the resistance of these cells to complement may be due to repair of transmembrane pores. Comparison of chromium-release assays with fluorescein diacetate dye uptake viability assays showed that human keratinocytes were still susceptible to monocyte and lymphocyte ADCC but not to antibody, antibody plus complement, or natural killing. The reproducible and uniform susceptibility of normal and transformed keratinocyte targets from three different species to monocyte and lymphocyte ADCC supports the hypothesis that this mechanism of cellular lysis may be important in antibody-associated diseases of epidermal cytotoxicity.
Alternative mechanism of protein A-immunoglobulin interaction the VH-associated reactivity of a monoclonal human IgM.
Authors: Vidal M A , Conde F P 
Published: December 2022

Abstract
The immunoglobulin site(s) that mediates the alternative mechanism of interaction between immunoglobulins and staphylococcal protein A (SpA) was studied by using a monoclonal human IgM. Several IgM fragments were tested for their inhibitory effect in a competitive binding assay of 125I-IgM to SpA. Only those fragments containing Fab mu pieces showed some inhibitory activity. The reactivity of the Fab mu region was retained in some of its subfragments, such as Fv or the VH domain, unlike isolated light chains or VL domains. Furthermore, antibodies specific for the VH domain completely inhibited the SpA-IgM interaction. These results indicate that the alternative SpA-binding site of IgM is located in VH regions.
T cell regulation of light chain expression: preferential enhancement of Ig kappa in a primary thymus-dependent response does not require affinity-based selection.
Authors: Burkly L C , Nikolic J , Wortis H H 
Published: December 2022

Abstract
Previously we reported that the proportion of Ig kappa to Ig lambda anti-DNP antibodies produced by day 5 of a primary response to thymus-dependent antigens was fivefold greater than the Ig kappa:Ig lambda ratios found in responses to thymus-independent antigens. To determine whether an affinity-based process explained the differences in kappa/lambda ratios seen, we measured the affinity of Ig kappa and Ig lambda antibody by using the binding ratio radioimmunoassay method, which measures the affinity of antibodies of particular isotypes without the need for prior purification. By the addition of a mild reduction step, the affinities of IgG and IgM antibody could be simultaneously measured. The affinity of day 5 Ig kappa anti-DNP evoked by DNP-KLH is not significantly higher than that of Ig lambda anti-DNP evoked by DNP-Ficoll, nor is it significantly different from that of Ig lambda antibody produced. As an alternative to affinity-based selection, it is suggested that T cells can preferentially augment Ig kappa responses.