bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of ADP-ribosylation of GTP-binding protein by pertussis toxin on immunoglobulin E-dependent and -independent histamine release from mast cells and basophils.
Authors: Saito H , Okajima F , Molski T F , Sha'afi R I , Ui M , Ishizaka T 
Published: December 2022

Abstract
Pretreatment of rat peritoneal mast cells, human basophils, bone marrow-derived mouse mast cells (BMMC) and mouse mast cell line PT-18 cells with 1 microgram/ml pertussis toxin (PT) failed to inhibit immunoglobulin E (IgE)-dependent histamine release from the cells. In BMMC and PT-18 cells, even 20-hr incubation of the cells with 1 microgram/ml PT, which ADP-ribosylates more than 97% of 41 kDa, alpha-subunit of Ni in the cells, failed to affect the IgE-dependent release of histamine or arachidonate. The results indicate that GTP-binding protein, Ni, is not involved in the transduction of triggering signals induced by cross-linking of IgE receptors. In contrast, pretreatment of rat mast cells with 1 ng/ml to 0.1 microgram/ml PT for 2 hr inhibited histamine release induced by compound 48/80 in a dose-dependent manner. A similar pretreatment with PT inhibited thrombin-induced histamine release from BMMC and N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced histamine release from human basophils in a similar dose-dependent fashion. However, even 20 hr of incubation of sensitized BMMC with 1 microgram/ml PT failed to inhibit either thrombin-induced or antigen-induced breakdown of phosphatidylinositides (PI), i.e., the formation of inositol triphosphate and diacylglycerol, Quin-2 signal, and the release of arachidonic acid. The results indicate that the inhibition of thrombin-induced histamine release by PT-treatment is not due to the inhibition of PI-turnover, and that Ni is not involved in thrombin-induced or antigen-induced (IgE-dependent) hydrolysis of phosphatidylinositides in mast cells.
Lepromin-induced lymphoproliferative response of experimental leprosy monkeys: regulatory role of monocyte and lymphocyte subsets.
Authors: Ohkawa S , Martin L N , Gormus B J 
Published: December 2022

Abstract
We investigated the immunological status of seven normal, control Mangabey monkeys and 23 Mangabey monkeys experimentally inoculated with Mangabey-origin Mycobacterium leprae. Clinically, these monkeys were divided into three broad groups: a recently inoculated group, a resistant group, and a susceptible group. The resistant group included 11 monkeys, seven of which showed no clinical sign of disease to date and four of which had shown local disease that partially regressed spontaneously. The susceptible group included eight monkeys, five of which have disseminated disease and three with local but stable disease. When peripheral blood mononuclear cells of these monkeys were cultured with Dharmendra-type human lepromin, one of seven normal monkeys, four of four of the recently inoculated group, seven of 10 resistant monkeys, and three of eight susceptible monkeys showed significant responses. In this experimental monkey model, we studied possible regulatory mechanisms by using OKT4- and OKT8-enriched lymphocytes, and Fc receptor-positive (FcR+) and FcR- monocyte (M phi) subsets. The OKT4+ subset was the main lepromin-responsive cell type. High percentages of OKT8+ cells showed a good negative correlation with the lymphoproliferative responses of T-enriched cells supplemented with unfractionated M phi. But the depletion of OKT8+ cells could not increase the response of nonresponding monkeys' lymphocytes. The resistant group and susceptible group did not differ in their percentages of OKT8+ cells. Because OKT8+ cells negatively regulate the response of lymphocytes and OKT4+ cells are the main responding cells, OKT8+ cells are phenotypically and functionally suppressor cells and OKT4+ cells are the helper/inducer cell population in this system. The FcR- M phi population mainly includes antigen-presenting activity, but high percentages of FcR- M phi showed a significant negative correlation with lymphoproliferative responses in the resistant group. A weak but significant lymphocyte response to Dharmendra lepromin was obtained by depleting FcR+ M phi from cultures of some susceptible monkeys, whereas lymphocytes of other susceptible monkeys remained unresponsive to lepromin. By these criteria, we could find an array of immunological defects in monkeys with experimental leprosy. The data suggest that some immunological defects may exist in the OKT4+ lymphocytes or FcR- M phi of leprosy monkeys.
Bacterial invasion of fibroblasts induces interferon production.
Authors: Hess C B , Niesel D W , Cho Y J , Klimpel G R 
Published: December 2022

Abstract
Although bacteria and/or bacterial products have been shown to induce interferon (IFN) production in cells of the immune system, the ability of non-lymphoid cells to produce IFN in response to bacterial products and/or bacterial invasion is currently unknown. In this study we examined murine and human fibroblasts for their ability to produce IFN in response to challenge with the invasive bacteria Shigella flexneri and enteroinvasive Escherichia coli. Both human and murine primary cell cultures produced high levels (500 to 1000 U/ml) of IFN-beta within 12 hr after Shigella invasion. The production of IFN appeared to be dependent upon bacterial invasion because no IFN was produced by cells pretreated with a non-invasive isogenic variant of S. flexneri. Furthermore, UV treated invasive S. flexneri, which lose the ability to invade cells, failed to induce IFN production in fibroblasts after bacterial challenge. In contrast to primary cells, most human and murine continuous cell lines did not produce IFN in response to Shigella invasion. The above results demonstrate that bacterial invasion of primary cultures of fibroblasts can induce IFN production. Taken together with previous findings, these results suggest that IFN may play an important front line host defense against invasive bacterial infections.
Enhanced lytic susceptibility of Ha-ras transformants after oncogene induction is specific to activated NK cells.
Authors: Johnson P W , Trimble W S , Hozumi N , Roder J C 
Published: December 2022

Abstract
C3H 10T1/2 mouse fibroblasts were transfected with a plasmid vector composed of EJ, the mutated c-Ha-ras, and a metallothionein promotor that induced amplified ras expression when activated by culture in the presence of zinc. Experiments were conducted to compare the effect of induction on killing by activated natural killer (NK) cells, cytotoxic T lymphocytes, activated macrophages, and antibody plus complement. The only effector that recognized increased ras expression and exhibited high-inducible cytolysis was an activated NK cell. The effectors from spleen were poly I.C. boostable, Lyt-1.1 negative, NK 1.2 positive, and asialo GM1 positive. Spleen cells from T cell-deficient nude mice, but not NK-deficient beige mice, exhibited high levels of killing activity, and experiments with NK cell clones demonstrated that these lines were also highly cytolytic and killed Ha-ras transfectants in parallel to YAC. Transfection of the same fibroblast line with c-myc did not alter the level of activated NK sensitivity. Cold target competition experiments revealed that Ha-ras-transfected and non-transfected 10T1/2 fibroblasts competed equally for lysis of either YAC or Ha-ras transfectants. Rat-1 fibroblasts did not compete, but gained this capacity when transformed with the v-Ki-ras oncogene but not v-fps. These data suggest that Ha-ras acts in target cells at a post-binding step, whereas Ki-ras may affect expression of target-effector binding structures. The findings that activated NK cell lysis may be specifically influenced by ras expression support a role for NK cells in host surveillance against early neoplastic changes.
Characterization of the antitumor activities of human tumor necrosis factor-alpha and the comparison with other cytokines: induction of tumor-specific immunity.
Authors: Palladino M A , Shalaby M R , Kramer S M , Ferraiolo B L , Baughman R A , Deleo A B , Crase D , Marafino B , Aggarwal B B , Figari I S 
Published: December 2022

Abstract
We have investigated the in vitro and in vivo antitumor activities of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) against Meth A sarcoma. Meth A sarcoma cells were found to a) be relatively insensitive in vitro to rHuTNF-alpha, and b) express low numbers of TNF-alpha receptors. Intraperitoneally implanted Meth A sarcoma was insensitive to the antitumor effects of rHuTNF-alpha. In contrast, rHuTNF-alpha was highly efficacious against subcutaneously implanted Meth A sarcoma. Biodistribution studies with 125I- or 3H-labeled rHuTNF-alpha demonstrated that, after intravenous administration, the majority of the labeled rHuTNF-alpha localized in the kidney, lungs, and liver. Only low levels of radiolabel were found in subcutaneous Meth A implants. These results support the in vitro data on the low number of TNF-alpha receptors on Meth A sarcoma cells. The ability of rHuTNF-alpha to induce regression of established (7 days) subcutaneous Meth A implants, positively correlated with the degree of both macroscopic and microscopic tumor necrosis. In addition, recombinant human tumor necrosis factor-beta (lymphotoxin) and recombinant murine tumor necrosis factor-alpha induced similar levels of necrosis. Other lymphokines with known antitumor activities, recombinant human interferon-gamma, murine interferon-gamma, and human interleukin 1 alpha, failed to induce detectable necrosis of Meth A sarcoma. Mice which had rejected subcutaneous Meth A sarcoma implants after rHuTNF-alpha treatment and which were later challenged subcutaneously with Meth A sarcoma or other noncross-reacting chemically induced sarcomas were found to be specifically immune to Meth A sarcoma. In addition, low levels of cytotoxic antibodies reactive to Meth A sarcoma were detected in the sera of 21 of 30 Meth A immune mice. Histological evaluation of the hemorrhagic tumor necrosis induced by rHuTNF-alpha suggests that the primary lesion is vascular, possibly directly on the endothelial cells. The mechanisms involved in the generation of specific cell-mediated antitumor immunity in this model are at present unknown.
In vivo immunosuppression by pan-T cell antibodies relates to their isotype and to their C1q uptake.
Authors: Kummer U , Thierfelder S , Hoffmann-Fezer G , Schuh R 
Published: December 2022

Abstract
There is considerable interest in the use of monoclonal anti-T cell antibodies for immunosuppression during organ transplantation. However, the in vitro cytotoxic titers of these monoclonal reagents do not correlate with their immunosuppressive potency when injected in vivo. A relationship nevertheless seems to exist between immunosuppression and the isotype of anti-mouse Thy-1 antibodies, because among several anti-Thy-1 antibodies of mouse and rat origin, the only two found to cause immunosuppression in vivo belonged to the rat IgG2b and mouse IgG2a isotype. We show here that a quantitative positive correlation exists between an antibody-induced humoral effector mechanism and immunosuppression. We measured the uptake of the C1q complement subunit by polyclonal rabbit and rat anti-thymocyte globulin and also seven monoclonal anti-Thy-1 antibodies in an immunohistochemical assay or a radioimmunoassay. Immunosuppression was studied in a murine graft-vs-host and skin allograft model. Our results suggest strongly that a stable association between the C1 protein and a potential binding antibody is an essential prerequisite of antibody-dependent cell inhibition in vivo that suppresses the immunoresponse against strongly incompatible transplantation antigens.
Functions of accessory cells in B cell responses to thymus-independent antigens.
Authors: Sinha A A , Guidos C , Lee K C , Diener E 
Published: December 2022

Abstract
The functions of adherent accessory (A) cells in thymus-independent (TI) B cell activation were investigated using homogeneous A cell lines with distinct cell surface and functional characteristics, as well as inhibitors of antigen processing and interleukin 1 (IL 1) secretion. B cell responses to both type 1 and type 2 TI antigens were found to be strictly A cell dependent. Only A cells capable of IL 1 secretion could restore responsiveness in A cell-depleted spleen cells, regardless of Ia expression or antigen-processing capability. Moreover, recombinant IL 1 completely replaced A cell function in B cell responses to both TI 1 and TI 2 antigens. Finally, T cell depletion did not diminish the reconstitution by IL 1. Thus in contrast to T cell activation, IL 1 secretion is the only A cell function required in TI B cell activation, and the data are consistent with a direct role for IL 1 in B cell activation.
Regulation by interferons of the local inflammatory response to bacterial lipopolysaccharide.
Authors: Heremans H , Dijkmans R , Sobis H , Vandekerckhove F , Billiau A 
Published: December 2022

Abstract
Footpad swelling developing in mice after local injection of LPS (S. marcescens) was found to consist of two phases with peaks occurring on days 2 to 3 and 6 to 8, respectively. Histopathologically, the reaction was characterized by edema and mononuclear cell infiltration; the second peak was associated with intravascular thrombosis as is typically described for the Shwartzman reaction to LPS. Recombinant DNA-derived IFN-gamma, administered by i.p. injection, had a suppressive effect on the development of the reaction. The same effect was seen with recombinant DNA-derived IFN-alpha 1 and with the natural mixture of IFN-alpha and -beta. In mice pretreated with neutralizing monoclonal antibodies to IFN-gamma, the footpad response to LPS was modified in that a delayed monophasic rather than a biphasic response occurred. These data indicate that LPS induces local production of IFN-gamma, which acts as a trigger or positive regulator of the reaction. The effect of a single pretreatment with neutralizing anti-IFN-gamma antibody was found to last for as long as 6 wk. Experiments in which antibody administration was delayed till after LPS challenge indicated that endogenous IFN-gamma was also involved in the late phases of the inflammation. The results show that regulation of inflammation by interferons is complex in that local IFN-gamma acts as a positive factor, whereas systemic IFN-alpha 1 and -gamma, probably through indirect mechanisms, downregulate inflammation.
Removal of glomerular deposits induced by either preformed immune complexes or by a chronic immune complex model in NZB/W mice.
Authors: Haakenstad A O 
Published: December 2022

Abstract
The solubilization and removal of defined glomerular immune complex deposits by excess antigen was examined in NZB/W female mice. Glomerular deposits were induced by administering preformed immune complexes to young (2 to 4 mo) mice before they naturally acquired deposits from endogenous disease and to old (7 mo) mice with deposits from naturally acquired disease. The administration of excess antigen specifically removed deposits of preformed immune complexes in both groups. This was associated with a reduction in circulating large latticed complexes containing more than two antigen and two antibody molecules (greater than Ag2Ab2). Established deposits in old mice therefore did not interfere with removal of newly induced deposits of preformed immune complexes. Glomerular deposits were also induced in young mice by a chronic human serum albumin (HSA) immune complex model. The antigen in immune deposits induced by 2 wk of chronic antigen administration was solubilized and was removed within 48 hr of administering excess antigen. Circulating antibodies to the antigen were also reduced by excess antigen. Glomerular deposits of mouse immunoglobulin and complement were not significantly reduced by excess antigen but remained more intense than in mice of comparable age given preformed complexes. Thus deposits of other antigen antibody systems and possibly endogenous disease were induced by the chronic HSA immune complex model in NZB/W mice. However, defined antigen deposits within deposits containing multiple antigen antibody systems can clearly be removed by administering excess antigen.
Immune complexes with cationic antibodies deposit in glomeruli more effectively than cationic antibodies alone.
Authors: Mannik M , Gauthier V J , Stapleton S A , Agodoa L Y 
Published: December 2022

Abstract
In previously published studies, highly cationized antibodies alone and in immune complexes bound to glomeruli by charge-charge interaction, but only immune complexes persisted in glomeruli. Because normal IgG does not deposit in glomeruli, studies were conducted to determine whether cationized antibodies can be prepared which deposit in glomeruli when bound to antigen but not when free in circulation. A series of cationized rabbit antiHSA was prepared with the number of added amino groups ranging from 13.3 to 60.2 per antibody molecule. Antibodies alone or in preformed soluble immune complexes, prepared at fivefold or 50-fold antigen excess, were administered to mice. With the injection of a fixed dose of 100 micrograms per mouse, antibodies alone did not deposit in glomeruli with less than 29.6 added amino groups by immunofluorescence microscopy. In contrast, 100 micrograms of antibodies with 23.5 added amino groups in immune complexes, made at fivefold antigen excess, formed immune deposits in glomeruli. With selected preparations of cationized, radiolabeled antibodies, deposition in glomeruli was quantified by isolation of mouse glomeruli. These quantitative data were in good agreement with the results of immunofluorescence microscopy. Immune complexes made at 50-fold antigen excess, containing only small-latticed immune complexes with no more than two antibody molecules per complex, deposited in glomeruli similar to antibodies alone. Selected cationized antibodies alone or in immune complexes were administered to mice in varying doses. In these experiments, glomerular deposition of immune complexes, made at fivefold antigen excess, was detected with five- to 10-fold smaller doses than the deposition of the same antibodies alone. These studies demonstrate that antibody molecules in immune complexes are more likely to deposit in glomeruli by charge-charge interactions than antibodies alone.
Human monoclonal multiple-organ-reactive autoantibodies distinguished by mouse monoclonal anti-idiotypic antibodies: expression of idiotopes in humans with and without autoimmune diseases.
Authors: Uchigata Y , Prabhakar B S , Salata K F , Ginsberg-Fellner F , Notkins A L 
Published: December 2022

Abstract
Previously we reported on the production and characteristics of a number of human monoclonal autoantibodies. All of these autoantibodies were of the IgM class and reacted with antigens in multiple organs. In this study we generated IgG murine monoclonal anti-idiotypic antibodies against five human monoclonal autoantibodies, (i.e., MOR-h2, MOR-h3, MOR-h4, CG1, and CG2). These anti-idiotypic antibodies reacted strongly with the corresponding human monoclonal autoantibody, but minimally or not at all with other human monoclonal autoantibodies. By using these anti-idiotypic antibodies as probes, we screened sera obtained from normal individuals and patients with insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and systemic lupus erythematosus for the expression of idiotopes. Our study showed that the idiotopes recognized by three of the anti-idiotypic antibodies, i.e., anti-CG1, anti-CG2, and anti-MOR-h2, were not expressed, but the idiotopes recognized by two of the anti-idiotypic antibodies, i.e., anti-MOR-h3 and anti-MOR-h4, were expressed in normal individuals. In patients with autoimmune disorders, there was no increase in the expression of the CG1, CG2, and MOR-h2 idiotopes, but 45 and 23% of the patients with systemic lupus erythematosus showed a significant increase in the expression of the MOR-h3 and MOR-h4 idiotopes respectively. These findings show that there is widespread expression in the B cell repertoire of certain autoantibody-associated idiotopes.
Expression of interleukin 1 receptors on human peripheral T cells.
Authors: Shirakawa F , Tanaka Y , Ota T , Suzuki H , Eto S , Yamashita U 
Published: December 2022

Abstract
The expression of interleukin 1 receptors (IL 1R) on human peripheral T cells was studied by the binding assay with 125I-labeled recombinant human interleukin 1 (IL 1) alpha and IL 1 beta and by the flow cytofluorometry with the fluorescein isothiocyanate (FITC)-conjugated IL 1 alpha. Peripheral blood lymphocytes expressed only few IL 1R without any stimulations. When they were stimulated with concanavalin A (Con A), IL 1R-positive cells began to increase by 4 hr, reached the maximum level at 48 hr, and then gradually decreased. The kinetics of the expression of IL 1 alpha R and IL 1 beta R showed the same pattern. Furthermore the binding of 125I-labeled IL 1 alpha to IL 1R on T cells was inhibited by the addition of either cold IL 1 alpha or IL beta, but not by interleukin 2 or interferons. The similar results were observed in the binding of 125I-labeled IL 1 beta. These results suggest that IL 1R on human peripheral T cells reactive for IL 1 alpha and IL 1 beta were identical. By Scatchard plot analysis, the numbers of IL 1R were estimated as 40 and 350 molecules per cell before and after Con A stimulation, respectively, and their Kd values were 3.1 X 10(-10) M and 2.8 X 10(-10) M. When purified T cells alone were stimulated with Con A, IL 1R were only marginally expressed. However, by the addition of monocytes, IL 1R were expressed on T cells in a dose-dependent manner. The maximum response was induced in the presence of 10% monocytes. The maximum IL 1R-positive T cells were approximately 30% by the detection of the flow cytofluorometry with FITC-conjugated IL 1 alpha. This enhancing activity of IL 1R expression on T cells by monocytes was inhibited by the addition of an anti-HLA-DR antibody or by the treatment of monocytes with the anti-HLA-DR antibody and complement. Furthermore T cell proliferative responses induced with IL 1 and Con A were also enhanced by the addition of HLA-DR-positive monocytes. These results suggest that IL 1R are expressed as the result of monocyte-T cell interaction in the early stage of T cell activation, and the expression of IL 1R on T cells and the responsiveness of T cells for IL 1 require the accessory function of HLA-DR-positive monocytes.