bluuebunny/crossref_metadata_2025_split huggingface dataset:
C5 gene influences the development of murine myasthenia gravis.
Authors: Christadoss P 
Published: December 2022

Abstract
The influence of the C5 gene and C5 deficiency on murine experimental autoimmune myasthenia gravis (EAMG) susceptibility was evaluated. Two co-isogenic strains, B10.D2/nSn (C5 sufficient) and B10.D2/oSn (C5 deficient), which are genetically identical except for the C5 gene locus, were immunized with acetylcholine receptors (AChR) in CFA to induce myasthenia gravis. Both strains had equivalent concentration of serum autoantibodies to muscle AChR and antibodies bound to muscle AChR. C5-sufficient B10.D2/nSn, but not C5-deficient B10.D2/oSn, demonstrated increased incidence of clinical disease and death and lost significant amounts of muscle AChR. Therefore, C5 deficiency in B10.D2/oSn prevented EAMG. C5 gene, which codes for C component C5, may influence EAMG pathogenesis through activation of the terminal lytic C sequence (C5 to C9) required for muscle AChR destruction, which is the primary pathology.
Monoclonal anti-idiotypic and anti-anti-idiotypic antibodies from mice immunized with a protective monoclonal antibody against Schistosoma mansoni.
Authors: Percy A J , Harn D A 
Published: December 2022

Abstract
To study the role of idiotypic anti-idiotypic interactions in schistosomiasis, mice were immunized with a mAb, E.1, which bound to soluble egg and larval stage Ag and also passively transferred resistance to cercarial challenge in mice. Subsequently, hybridomas were produced from E.1 immunized mice and tested for the ability to inhibit E.1 binding to soluble egg Ag. The results showed that anti-idiotypic mAb (Ab2) were produced. The range of inhibitory activity was from 33 to 100%. By using a direct Ab2 binding assay, the Ab2 were shown to be idiotypic specific, not isotype specific. It was also found that six of the hybridomas bound to soluble egg Ag and were therefore anti-anti-idiotypic antibodies (Ab3). Ab3 were shown to be inhibited from binding to soluble egg Ag by Ab2. To the authors' knowledge, this is the first time that an in vivo network relevant to an infectious organism has been reproduced in vitro such that both Ab2 and Ab3 were produced from the same animals independent of exposure to parasite Ag.
Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing.
Authors: Manca F , Fenoglio D , Kunkl A , Cambiaggi C , Sasso M , Celada F 
Published: December 2022

Abstract
We have used the enhanced uptake by FcR-bearing cells observed when Ag is administered as an immune complex to investigate the possible impact of specific antibodies on processing and presentation of antigen by accessory cells. The Ag Escherichia coli beta-galactosidase alone or bound to different mAb was incubated with peritoneal macrophages. These were subsequently exposed to a battery of Ag-specific T hybridoma clones. The resulting production of IL-2 was taken as a measure of effective presentation. The results of 43 mAb-T clone combinations showed a potentiation of presentation of Ag at substimulatory concentration in the majority of the cases, indicating that each mAb is conducive to FcR-mediated uptake by macrophages, and that each T clone can be stimulated by properly presented Ag. In contrast, nine combinations yielded a lower response, two of them falling to baseline values. We attribute these results, which corroborate our previous evidence of directional help in the beta-galactosidase system, to a modulation in enzymatic processing of Ag and its subsequent presentation imposed by the paratope of the mAb binding to the relevant epitope.
Angiotensin II (AII)-related idiotypic network. I. Common occurrence of AII internal image on rabbit anti-idiotypic antibodies.
Authors: Pontillon F , Moullier P , Ronco P M , Verroust P J 
Published: December 2022

Abstract
Internal images of foreign Ag have been demonstrated in a variety of systems as anticipated by the idiotypic network theory formulated by Jerne. However, they seem to be of rare occurrence. In order to estimate the actual frequency of antibodies bearing internal images (Ab2-beta) of angiotensin II (AII), a phylogenetically conserved peptide made up of eight amino acids, nine rabbits were immunized with affinity or protein A purified anti-AII antibodies (Ab1) from allotype-matched rabbits. Four of nine antiidiotypic antibodies (Ab2) exhibited internal image-like reactivity. They recognized all the polyclonal Ab1 tested, whatever the species (rabbit, mouse, guinea pig). In addition, they were strongly reactive with three mAb specific for a carboxy terminus epitope on AII (mAb 110, 199, and 211) and with a fourth monoclonal Ab1 (133) identifying a more central epitope. Advantage was taken of this reactivity with mAb1 to purify Ab2-beta by affinity chromatography of Ab2 on Sepharose 4B covalently linked to the three monoclonal Ab1 specific for the carboxy terminus epitope. The eluate displayed typical internal image properties: 1) it reacted with all the polyclonal Ab1 tested, 2) this reaction was completely abolished by AII, and 3) rabbits and mice immunized with the eluate all produced Ab1. The AII related idiotypic network is thus characterized by high frequency and immunogenicity of AII internal images. In addition, reactivity of the latter with monoclonal Ab1 indicates variable expression on Ab2-beta of the epitopes defined by the mAb on the nominal Ag.
Macrophages isolated from liver granulomas of murine Schistosoma mansoni synthesize predominantly TxA2 during the acute and chronic phases of infection.
Authors: Tripp C S , Needleman P , Kassab J T , Weinstock J V 
Published: December 2022

Abstract
Macrophages isolated from liver granulomas of mice infected with Schistosoma mansoni for 8 or 20 wk synthesize predominantly thromboxane A2 with smaller amounts of the PGE2 and PGI2. There is no physiologic production of leukotrienes, as determined by RIA and HPLC. Thromboxane A2 is the predominant arachidonic acid metabolite whether the cells are stimulated by a phagocytic stimuli such as zymosan or the exogenous substrates arachidonic acid and PGH2. These data indicate that the predominant arachidonate enzymatic activity in these cells is thromboxane synthase.
Differential activation requirements for virgin and memory T cells.
Authors: Byrne J A , Butler J L , Cooper M D 
Published: December 2022

Abstract
Most studies of the activation requirements for T cells have used either T cell lines or populations of normal T cells that consist of a mixture of virgin and Ag-primed T cells. These two subpopulations of T cells can now be distinguished in humans by their reactivity with mAb. The anti-CD45R antibody HB10 identifies virgin T cells (T degrees) that are non-reactive to recall Ag and relatively poor at providing help for B cell differentiation. Conversely, memory T cells (T') that can react to recall Ag and enhance Ig production are non-reactive with anti-CD45R, but can be identified with the UCHL1 antibody. We have used these antibodies to separate the T degrees and T' populations and examine their activation requirements. On activation CD45R+ cells rapidly began to lose the CD45R Ag and express the UCHL1 Ag in increased amounts, whereas the UCHL1+ cells retained this phenotype. Both populations responded to PHA in the presence of monocytes, but when triggered by an antibody to CD3 only the T' cells were induced to express IL-2R, produce IL-2, and to proliferate. The T degrees population of cells remained relatively quiescent by all of these parameters. However, anti-CD3 stimulation conditioned the T degrees cells for IL-2 responsiveness, inasmuch as the addition of rIL-2 resulted in significant IL-2R expression and proliferation. When the CD4+ T degrees and CD4+ T' subpopulations were isolated and examined in the same assays similar results were obtained. The data indicate that fundamental differences exist in the triggering requirements for T degrees and T' cells.
Construction of antigen-specific suppressor T cell hybridomas from spleen cells of mice primed for the persistent IgE antibody formation.
Authors: Iwata M , Ishizaka K 
Published: December 2022

Abstract
Attempts were made to generate Ag-specific suppressor T cells from Ag-primed spleen cells by using glycosylation inhibiting factor (GIF). BDF1 mice were primed with alum-absorbed OVA and their spleen cells were stimulated with OVA. Ag-activated T cells were then propagated in IL-2-containing conditioned medium. Incubation of the T cells with OVA-pulsed syngeneic macrophages resulted in the formation of IgE-potentiating factor and glycosylation-enhancing factor that has affinity for OVA, i.e., OVA-specific glycosylation-enhancing factor. However, if the same Ag-activated splenic T cells were propagated in the IL-2-containing medium in the presence of GIF T cells obtained in the cultures formed IgE-suppressive factors and OVA-specific GIF on antigenic stimulation. Thus we constructed T cell hybridomas from the Ag-activated T cells propagated by IL-2 in the presence of GIF. A representative hybridoma, 71B4, formed OVA-specific GIF on incubation with OVA-pulsed macrophages of BDF1 mice or C57B1/6 mice. However, if the same hybridoma cells were incubated with OVA alone or with OVA-pulsed macrophages of H-2k or H-2d strains, they produced GIF that had no affinity for OVA. The OVA-specific GIF bound to OVA-Sepharose but did not bind to BSA-Sepharose or KLH Sepharose. Intravenous injections of the OVA-specific GIF from the hybridoma suppressed the IgE and IgG1 anti-DNP antibody response of BDF1 mice to DNP-OVA, but failed to suppress the anti-hapten antibody responses of the strain to DNP-keyhole limpet hemocyanin, indicating that the factors suppressed the antibody response in a carrier-specific manner. However, the same OVA-specific GIF failed to suppress the anti-hapten antibody response of DBA/1 mice to DNP-OVA, suggesting that the immunosuppressive effects of the factors is MHC restricted.
Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells.
Authors: Ogasawara M , Iwabuchi K , Good R A , Onoe K 
Published: December 2022

Abstract
When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance.
Selective inhibition of antigen presentation to cloned T cells by protease inhibitors.
Authors: Puri J , Factorovich Y 
Published: December 2022

Abstract
The effect of eight microbial protease inhibitors on Ag-presentation to six different Ag-specific T cell clones was investigated. We found that these protease inhibitors can inhibit Ag presentation in a highly selective manner. This selectivity was evident with T cell clones specific to different Ag as well as with T cells specific to the same Ag but differing in their H-2 restriction. The inhibition was to due to cytotoxicity or effects through the TCR because none of the eight inhibitors inhibited IL-2-induced T cell proliferation, and because they did not inhibit Ag presentation by fixed APC or synthetic polypeptide. The conclusion after these data suggests that each specific antigenic fragment is produced by a unique set of proteases.
In vivo and in vitro production of IFN-beta and IFN-gamma during graft vs host disease.
Authors: Cleveland M G , Annable C R , Klimpel G R 
Published: December 2022

Abstract
We have shown previously that high levels of IFN-beta were generated in vitro from spleen cells obtained from mice experiencing graft vs host disease (GVHD). However, very little or no IFN-gamma was found in these cultures even when IL-2 or Con A was added as a stimulant of IFN-gamma production. This study was undertaken to determine if the IFNs were similarly produced in vivo during the GVH reaction and to further explore the inability of GVHD spleen cells to produce IFN-gamma in vitro. GVHD was induced across minor histocompatibilities by the i.v. injection of B10.D2 spleen cells into sub-lethally irradiated BALB/c mice. Using cytoplasmic immunofluorescence to detect IFN-beta and -gamma, both IFNs were readily detectable in vivo in spleens of mice undergoing GVHD. IFN-gamma demonstrated a distinct distribution pattern, localizing in the peri-arteriolar lymphoid regions of the spleen, whereas IFN-beta immunofluorescence appeared diffusely in all areas. Expression of both IFN-beta and -gamma was shown to be dependent on the GVH reaction, inasmuch as syngeneic controls and mice given T cell-depleted donor cells had little immunofluorescence. These results contradict in vitro data in that IFN-gamma cannot be found in GVHD spleen cell cultures even in the presence of Con A. This in vitro unresponsiveness appeared to be due to the mixing of different cell populations as a result of preparing splenic single-cell suspensions. Percoll gradient fractionation of GVH spleen cells yielded a cell population which, when stimulated with Con A, produced IFN-gamma and underwent cell proliferation. This study represents the first description of the in vivo splenic distributions of IFN-beta and -gamma during GVHD, and presents data that suggest that in vitro results may not truly reflect in vivo immune responsiveness. Thus, the IFNs may play a critical role in the complex events leading to the GVHD syndrome.
Lethal graft-vs-host disease induced by a class II MHC antigen only disparity is not mediated by cytotoxic T cells.
Authors: Thiele D L , Bryde S E , Lipsky P E 
Published: December 2022

Abstract
Treatment of C57BL/6J (B6) murine splenocytes with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) selectively removes NK cells, CTL precursors, and the capacity to cause lethal graft-vs-host disease (GVHD) in irradiated B6 X DBA/2 F1 mice. In contrast, alloantigen-induced L3T4(+) Th cell function has been shown to be relatively preserved after exposure to this agent. The present studies assessed the effects of Leu-Leu-OMe treatment of donor cells on induction of lethal GVHD in other murine strain combinations. When irradiated B6 X CBAF1 mice were infused with T and NK cell-depleted B6 bone marrow cells and 3 to 30 X 10(6) B6 spleen cells, uniformly lethal GVHD was observed. However, B6 X CBAF1 recipients of T and NK-depleted B6 bone marrow cells and similar numbers of Leu-Leu-OMe-treated B6 spleen cells demonstrated 90 to 100% long term survival. In contrast, Leu-Leu-OMe treatment of B6 donor cells had no beneficial effect on mortality rates in irradiated (B6 X B6-C-H-2bm12)F1 (B6 X bm12F1) recipients. When B6 spleen cells were stimulated in vivo or in vitro with either B6 X CBAF1 or B6 X bm12F1 stimulator cells, the capacity to generate alloantigen-specific CTL was abolished comparably by Leu-Leu-OMe treatment. Thus, the dramatic difference between the effects of Leu-Leu-OMe treatment of B6 spleen cells on the course of GVHD in B6 x CBAF1 and class II MHC only disparate B6 x bm12F1 recipients could not be explained by unique resistance of bm12-specific CTL precursors to Leu-Leu-OMe. These findings indicate that T cell effector mechanisms distinct from classic cell-mediated cytotoxicity are sufficient to generate lethal GVHD in class II MHC only disparate B6----B6 X bm12F1 mice.
Effects of granulocyte-macrophage colony-stimulating factor and colony-stimulating factor-1 on the proliferation and differentiation of murine alveolar macrophages.
Authors: Akagawa K S , Kamoshita K , Tokunaga T 
Published: December 2022

Abstract
Murine alveolar macrophages (AM) were shown to have proliferative ability and to form colonies in vitro. The factors in lung-conditioned medium (CM) and L929-CM which stimulate the proliferation of AM were considered to be granulocyte-macrophage colony-stimulating factor (GM-CSF) and CSF-1, respectively, because recombinant murine (rm)GM-CSF and recombinant human (rh)CSF-1 could replace the activities of lung-CM and L929-CM, respectively. The phenotype of the cells in the colonies formed by AM incubated with rmGM-CSF or lung-CM was AM-like; more than 90% of the cells were stained by anti-asialo GM1 but not by FITC-LPS, and had AM-like morphology. Expression of Mac-1 Ag determined by M1/70HL in these cells as well as original AM was low. However, the phenotype of the cells in the colonies formed by AM incubated with rhCSF-1 or L929-CM was peritoneal macrophage (PM)-like; more than 90% of the cells were stained by FITC-LPS and M1/70HL, but not by anti-asialo GM1, and showed PM-like morphology. The cells in the colonies formed by AM incubated with rmGMCSF changed their phenotype after treatment with rhCSF-1; the percentage of cells stained by anti-asialo GM1 decreased, and that of cells stained by FITC-LPS increased. The cells in the colonies formed by AM incubated with rhCSF-1 never changed their phenotype after incubation with rmGM-CSF. In contrast to AM, more than 90% of the cells in all colonies formed by PM incubated with either rmGM-CSF, rhCSF-1, lung-CM, or L929-CM were stained by FITC-LPS but not by anti-asialo GM1. These results show that although AM and PM can proliferate, AM, in contrast to PM, are bipotential cells that can differentiate into two types of macrophages responding to distinct types of CSF, and that one of the molecular mechanisms controlling macrophage heterogeneity may be based on the type of CSF produced at distinct tissues.
Tumor necrosis factor-alpha and tumor necrosis factor-beta (lymphotoxin) stimulate the production of granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in vivo.
Authors: Kaushansky K , Broudy V C , Harlan J M , Adamson J W 
Published: December 2022

Abstract
A number of cell types have been shown to elaborate hematopoietic growth factors in response to inflammatory mediators in vitro. To determine if this response occurs in vivo, we have administered levels of TNF-alpha and TNF-beta (lymphotoxin) found during an inflammatory reaction to mice. Using Northern blot analysis to detect tissue levels of hematopoietic growth factor-specific transcripts, and specific biologic and immunologic assays to detect the presence of colony-stimulating factors in the serum, we have found that TNF-alpha and TNF-beta induce the transcription and production of granulocyte-macrophage-CSF, macrophage-CSF, and IL-1. These findings provide an in vivo mechanism for the hematopoietic response to inflammation.
Molecular analysis of the gene encoding the major surface antigen of Toxoplasma gondii.
Authors: Burg J L , Perelman D , Kasper L H , Ware P L , Boothroyd J C 
Published: December 2022

Abstract
The complete sequence of P30, the major surface Ag of the protozoan parasite, Toxoplasma gondii, has been deduced through the cloning and analysis of its gene. Using polyclonal serum specific for P30, we have isolated a P30 cDNA clone from a lambda gt11 cDNA expression library derived from tachyzoites of T. gondii (RH strain). This clone produces a beta-galactosidase fusion protein which reacts with several anti-P30 mAb. In addition, polyclonal anti-serum raised to the fusion protein reacts with purified P30 protein and exclusively with P30 in a whole cell lysate of T. gondii. This cDNA clone was used to isolate near full-length cDNA molecules and a cosmid clone containing the P30 gene. Sequence analysis of the cDNA reveals a single open reading frame with coding capacity for 34.7 kDa of primary translation product (consistent with the apparent Mr of P30 on SDS-acrylamide gels) including a presumptive hydrophobic signal sequence. The P30 primary translation product also has a carboxy-terminal hydrophobic tail which is predictive of a posttranslational cleavage and modification with a glycolipid anchor. We have identified the apparent 5' and 3' ends of the P30 mRNA transcript which is extremely abundant, 1500 nucleotides in length, and polyadenylated. The P30 gene is single copy and contains no introns.
Patterns of Ig V region expression among neonatal hemagglutinin-responsive B cells. Evidence for non-random VH gene representation during later stages of development.
Authors: Kienker L J , Korostoff J M , Cancro M P 
Published: December 2022

Abstract
Hybridoma libraries were established whose specificities reflect those within the BALB/c hemagglutinin-responsive B cell repertoire at 1 or 2 wk of age. These libraries were generated through chronic immunization regimes that induce responses dominated by clonotypes available at the age of initial immunization. Dot blot analyses of cytoplasmic RNA from these hybridomas were performed to determine the Ig H chain V region (VH) families associated with the repertoire at each age. Although genes from most known VH families can generate hemagglutinin-specific antibodies, clonotypes prevalent during the first week of life disproportionately use VH7183 gene segments. In contrast, hybridomas representative of the repertoire in 2-wk-old individuals preferentially use VHS107, VH36-60, and VHX24 gene segments. These results demonstrate changes in VH gene family predominance that correlate with the age-related patterns of clonal emergence and turnover previously shown in the hemagglutinin-reactive B cell pool. Taken together, these findings suggest that the very early neonatal Ag-responsive B cell pool closely reflects preferential VH gene rearrangements within the pre-B cell compartment. Further, they suggest that either non-random strategies of VH gene expression, or selective clonal expansion strategies based on VH, operate even at later stages of development.
Isolation and analysis of murine serum amyloid P component cDNA clones.
Authors: Mole J E , Beaulieu B L , Geheran C A , Carnazza J A , Anderson J K 
Published: December 2022

Abstract
In contrast to other animals, the biosynthesis of serum amyloid P component in mice is regulated as an acute-phase protein. As a first step in studying the regulation and biosynthesis of serum amyloid P component in the mouse, cDNA clones have been isolated from a liver cDNA library and sequenced. The largest of these clones was 960 bp in length, and contained an open reading frame encoding a protein of 224 amino acids. Comparison of the mouse cDNA sequence to that published for humans (Mantzouranis, E. C., S. B. Dowton, A. S. Whitehead, M. D. Edge, G. A. P. Bruns, and H. R. Colten, 1985. J. Biol. Chem. 260:7752.) revealed 74% identity for nucleotides in the translated region. Northern-blot analysis demonstrated that murine serum amyloid P component synthesis in the liver is directed by a 1.2-kb mRNA that is elevated in high responder (C57BL/6J) mice after thioglycollate-induced inflammation.