bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of antibody-dependent cell-mediated cytotoxicity of human neutrophils and eosinophils by separate colony-stimulating factors.
Authors: Vadas M A , Nicola N A , Metcalf D 
Published: December 2022

Abstract
Semi-purified human colony-stimulating factors (CSF) powerfully enhanced the antibody-dependent cell-mediated cytotoxicity (ADCC) by metrizamide gradient-purified human neutrophils and eosinophils. The stimulation was observed on three different tumor targets, was rapid (less than 1 hr) in onset, and CSF-stimulated cells needed direct contact with targets for killing. A subspecies of human CSF, CSF-alpha, with eosinophil and granulocyte-macrophage (GM) colony-stimulating activity enhanced both eosinophil and neutrophil killing. In contrast, another subspecies of human CSF, CSF-beta, having only GM colony-stimulating activity, only enhanced neutrophil-mediated ADCC. These results support the notion that human CSF have two sites of action: i) the progenitor cell, where they stimulate a relatively slow process of differentiation, and ii) the mature cell, where they have a rapid action of increasing functional capacity. Furthermore, it seems the pattern of CSF receptors on progenitor cells is maintained throughout the lineage of such cells and serves to regulate the function of mature cells.
The extracellular region of light chains from human and murine MHC class II antigens consists of two domains.
Authors: Kaufman J F , Strominger J L 
Published: December 2022

Abstract
The experiments in this report, together with previous studies, demonstrate that the light chains of DR antigens are composed of four domains: two large extracellular domains (each with a disulfide loop), a short hydrophobic membrane-binding region, and a short hydrophilic carboxy-terminal domain. The amino-terminal extracellular domain is glycosylated and polymorphic and has no discernible sequence homology to immunoglobulin, whereas the relatively conserved carboxy-terminal extracellular domain bears striking homology to immunoglobulin. One chymotryptic and two tryptic cleavage sites lie in the second extracellular domain of the light chain of all native DR antigens. These three sites are found in loops at the same end of an immunoglobulin-like domain. The light chain of DC1 antigen lacks one of the tryptic cleavage sites; the DR heavy chain, the class I heavy chain, and beta 2 microglobulin lack all three proteolytic sites. Proteolysis of murine la antigens with chymotrypsin and trypsin generates similar fragments (I-E-like DR, I-A-like DC1) suggesting these cleavage sites are a general feature of class II antigen light chains.
Regulation of neutrophil inflammatory mediator release: chemotactic peptide activation of stimulus-dependent cytotoxicity.
Authors: English D , Lukens J N 
Published: December 2022

Abstract
Human neutrophils stimulated with phorbol myristate acetate (PMA) were able to damage human erythroleukemic K-562 target cells as assessed by a 3-hr 51Cr-release assay. Neutrophils from a patient with chronic granulomatous disease of childhood were ineffective in mediating PMA-stimulated cytolysis. Cytotoxicity was inhibited under anaerobic conditions as well as by catalase and several free radical scavengers. Superoxide dismutase, azide, and cyanide failed to inhibit PMA-dependent cytotoxicity. The influence of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) on stimulus-dependent cytotoxicity was examined. Neutrophils preincubated with 1.0 X 10(-7) M FMLP did not display an increased cytotoxic response, but were markedly amplified in their ability to effect cytotoxicity with the addition of PMA. Enhancement of PMA-stimulated cytotoxicity resulted from a reversible cellular response to FMLP. The kinetics of the cytotoxic responses reflected the possibility that chemotactic peptide-treated neutrophils released cytotoxic mediators to a greater extent and at a faster rate than did untreated neutrophils. Although azide and superoxide dismutase did not inhibit cytotoxic responses of chemotactic peptide-activated neutrophils, the response was prevented by catalase and was markedly inhibited by several free radical scavengers. The ability of FMLP to enhance cytotoxic responses correlated well with its enhancement of PMA-stimulated chemiluminescence under a variety of conditions. In addition, the ability of PMA-stimulated neutrophils to mediate methane generation from dimethyl sulfoxide and ethylene generation from alpha keto-gamma-methiol-butyric acid (KMB)--assays that quantitate the generation of oxidizing radicals--was increased if the neutrophils were preincubated with FMLP. These results demonstrate that a chemotactic factor greatly potentiates the release of cytotoxic mediators from neutrophils upon stimulation with a nonchemotactic agent. The cytotoxic mediators appear to be products of oxidative metabolism. The cytotoxic potential of neutrophils that have responded to chemotactic stimuli to reach sites of inflammation may be activated in a similar manner.
C3 cleavage products stimulate release of prostaglandins by human mononuclear phagocytes in vitro.
Authors: Rutherford B , Schenkein H A 
Published: December 2022

Abstract
Human monocytes cultured for up to 48 hr in serum-free, chemically defined culture media released low levels of prostaglandin. C3b, C3bi, and C3c stimulated an indomethacin-sensitive, dose-responsive increase in the amount of monocyte prostaglandin released by 18 hr after treatment. Native C3 and C3d, which do not bind to monocyte receptors, failed to stimulate increased prostaglandin release. Lymphocytes, treated and untreated, produced 10(-2) to 10(-3) as much prostaglandin as the monocytes. These data support the concept that monocytes are a significant source of leukocyte prostaglandin. They also introduce an important new biologic function for the C3 fragments C3b, C3bi, and C3c.
Requirements for the opsonic activity of human IgG directed to type 6 group A streptococci: net basic charge and intact Fc region.
Authors: Fischetti V A 
Published: December 2022

Abstract
By two independent techniques for separating human opsonic IgG for group A type 6 streptococci into fast- and slow-migrating fractions, it was found that the opsonic activity was localized within the basic charge population. This charge dependence was found to be a characteristic of the IgG isolated from three individuals. When the fast- and slow-migrating IgG fractions were tested for their ability to bind to purified M6 protein, antibodies in both opsonic and nonopsonic populations exhibited binding activity, with the majority being located within the opsonic IgG in two of the three individuals; the third displayed greater binding in the nonopsonic population. The functional difference observed in the antibody populations to this M antigen may be a reflection of the net charge within the area of the antibody binding site, which suggests that the opsonic antibodies need to bind to acidic residues along the outer surface of the fibrillar M protein molecule. F(ab')2 fragments prepared from both human and rabbit type 6 opsonic IgG were still able to bind to the M6 molecule but were unable to mediate opsonization of type 6 streptococci. However, the F(ab')2 fragments had the capacity to enhance or amplify the opsonic activity of low concentrations of opsonic IgG molecules. The results suggest that the M protein molecule may function as an active inhibitor of phagocytosis and that F(ab')2 fragments from opsonic IgG have the capacity to neutralize the "active" determinants on the molecule, thus allowing lower concentrations of IgG with functional Fc receptors to mediate phagocytosis.
Inhibition of mitogen-induced proliferation of mouse T and B lymphocytes by bloodstream forms of Trypanosoma cruzi.
Authors: Maleckar J R , Kierszenbaum F 
Published: December 2022

Abstract
The role of virulent forms of Trypanosoma cruzi in modulating mitogen-induced lymphocyte responses was investigated in this work. Bloodstream forms of T. cruzi inhibited normal mouse spleen cell responses to Con A and LPS in a dose-dependent manner. Reduced responses were observed over relatively large ranges of concentration of Con A (50-fold) and LPS (160-fold). The inhibitory action of the parasites could not be overcome by increasing the mitogen dose beyond optimal levels. Furthermore, absorption of mitogen solutions with four times as many parasites as used in the proliferation assays revealed that sufficient mitogen activity remained to produce optimal lymphocyte responses. Therefore, reduced lymphocyte responsiveness was not due to absorption of mitogen by the parasite. Inhibited responses were also seen when a sonicated T. cruzi preparation was used, indicating that parasite viability was not required to produce suppression. Inhibition of Con A- or LPS-induced responses by the parasites occurred only when the trypanosomes were incorporated into the system during the first 24 hr of culture. These results show that virulent forms of T. cruzi can induce suppression of T and B cell responses in vitro, and suggest that the parasite affects lymphocyte commitment to blastogenesis during the early stages of lymphocyte activation.
5-halo-6-phenyl pyrimidinones: new molecules with cancer therapeutic potential and interferon-inducing capacity are strong inducers of murine natural killer cells.
Authors: Lotzová E , Savary C A , Stringfellow D A 
Published: December 2022

Abstract
We tested the effect of three different interferon-(IFN) inducing pyrimidinone molecules with cancer therapeutic potential on natural killer (NK) cells. Peritoneal exudate (PE) cells were selected for these studies because their NK cell cytotoxicity is very low. Augmentation of PE-NK cell cytotoxicity was observed in eight different strains of mice after i.p. administration of 250 mg/kg of each of the pyrimidinones. NK cell induction occurred as early as 6 hr after pyrimidinone administration and peaked 2 to 4 days after treatment; at that time, cytotoxicity was as high as 60 to 90%. Augmentation of NK cell activity was independent of IFN serum levels induced by pyrimidinones and murine H-2 haplotype, and did not exhibit any histocompatibility or species-specific restriction, because it was expressed to syngeneic, allogeneic, and xenogeneic tumor target cells. Characterization studies demonstrated that the cytolytic cells were not macrophages, T cells, or B cells and exhibited NK cell characteristics. NK cell tumor-binding and tumor-killing studies demonstrated that NK cell augmentation was accomplished via both activation and recruitment of NK cells. If one considers NK cells as an important part of tumor immunity (as indicated by murine studies), pyrimidinone molecules may be effective anticancer agents.
Macrophage cell cycling: influence on Fc receptors and antibody-dependent phagocytosis.
Authors: Gandour D M , Walker W S 
Published: December 2022

Abstract
The influence of cell cycling on the density and binding properties of IgG2a Fc receptors and their associated antibody-dependent phagocytic activity was investigated with the P388D1 murine macrophage cell line. Unseparated macrophages and subpopulations of elutriated macrophages, enriched for cells in G1, S, and G2 + M phases were compared to detect possible differences in IgG2a-dependent phagocytosis. Suspensions of G2 + M phase cells were appreciably enhanced in phagocytic activity over G1-phase cells, which were less phagocytic than unseparated macrophage populations. An analysis of the binding of 125I-IgG2a myeloma protein disclosed that the IgG2a Fc receptor avidity remained essentially unchanged during cell cycle traverse, whereas the number of IgG2a Fc receptors more than doubled as cells cycled from G1 to G2 + M (1.5 X 10(5) vs 3.4 X 10(5) receptors per cell). With their increased size relative to G1 cells, and the resultant increase in receptor number, G2 phase cells should have more productive collisions with the antibody-coated target cells and greater phagocytic capacity.
Alveolar macrophages in pulmonary immune responses. I. Role in the initiation of primary immune responses and in the selective recruitment of T lymphocytes to the lung.
Authors: Lyons C R , Lipscomb M F 
Published: December 2022

Abstract
Antigen inoculated intratracheally (IT) into animals can induce primary immune responses and selectively recruit specific T cells to the lung. In the current study, the role of alveolar macrophages (AM) in these two responses was investigated. Antigen-pulsed bronchoalveolar cells (BAC) inoculated IT into guinea pigs generated a population of immune T cells that proliferated in vitro on reexposure to antigen-pulsed macrophages (Mø). The possibility that antigen-pulsed donor BAC shed antigen that was subsequently processed and presented by host Mø was ruled out by genetic experiments. Thus, peritoneal exudate lymphocytes (PEL) from (2 X 13)F1 guinea pigs primed with antigen-pulsed BAC from strain 2 animals responded preferentially to antigen-pulsed strain 2 Mø rather than to antigen-pulsed strain 13 Mø. In a second set of studies, antigen-pulsed BAC inoculated IT into guinea pigs selectively recruited antigen-specific T cells to the lung. Genetic experiments verified that inoculated BAC were the source of the antigen-presenting cells responsible for selective recruitment. Thus, antigen-pulsed strain 2 BAC inoculated IT recruited a greater proportion of (2 X 13)F1 T cells that recognized antigen in the context of strain 2 Mø than F1 T cells that recognized antigen on strain 13 Mø. Taken together, these studies suggest that AM contribute to the regulation of pulmonary immunity by both inducing T lymphocyte immunity and selectively recruiting specific T cells to the lung.
Inhibition of interleukin synthesis and T cell proliferation by a monoclonal anti-Ia antibody.
Authors: Gilman S C , Rosenberg J S , Feldman J D 
Published: December 2022

Abstract
The proliferative response in vitro of Lewis rat spleen cells to Con A was inhibited by a monoclonal antibody, OX4, with specificity for a public rat la antigen. Inhibition was dose-dependent and was observed only if the antibody was present during the first 48 hr of culture. OX4 anti-la antibody inhibited production of IL 1 by peritoneal exudate cells activated by lipopolysaccharide and inhibited the production of IL 2 by spleen cells activated by Con A. Addition of exogenous IL 1 to spleen cell cultures inhibited by OX4 anti-la antibody augmented production of IL 2 and returned the proliferative response of T cells to levels observed in Con A-stimulated cultures. We suggest that OX4 anti-la antibody reacts with la+ accessory cells to inhibit production of IL 1, which in turn limits production of IL 2 and finally T cell proliferation.
Fibroblast stimulation in schistosomiasis. IV. Isolated egg granulomas elaborate a fibroblast chemoattractant in vitro.
Authors: Wyler D J , Postlethwaite A E 
Published: December 2022

Abstract
Hepatic fibrosis complicates the chronic granulomatous inflammatory reaction to Schistosoma mansoni eggs, and is the major cause of morbidity and mortality in human schistosomiasis. We previously presented evidence that schistosomal egg granulomas secreted factors that can stimulate fibroblast proliferation and collagen synthesis in vitro. We now report that serum-free supernatants from cultures of hepatic egg granulomas isolated from S. mansoni-infected mice contained activity that stimulated the directional migration of human and guinea pig dermal fibroblasts in modified Boyden chambers. This fibroblast chemotactic activity was also detected in culture supernatants of granuloma adherent cells highly enriched for macrophages (95% latex-ingesting) but not in culture supernatants from resident peritoneal macrophages of uninfected or infected mice. This suggests that granuloma macrophages are a source of the chemotactic activity. The chemoattractant had the properties of large molecular weight (greater than 200,000 daltons; Sephadex G-200 gel filtration), pl approximately 4.5 (preparative flatbed isoelectrofocusing in granular matrix), heat stability (56 degrees C; 45 min), and trypsin sensitivity. Since preincubation of the partially purified granuloma and adherent-cell derived chemoattractants with rabbit anti-human fibronectin antibody abolished their chemotactic activity, it appears that the factor is antigenically similar to fibronectin. We propose that egg granuloma macrophages are activated in vivo to secrete a fibronectin-like molecule with activity that stimulates the directional migration of fibroblasts. This factor may therefore play a role in the local recruitment of fibroblasts and, in concert with other granuloma-derived factors, may play an important role in the pathogenesis of hepatic fibrosis in schistosomiasis.
Cytotoxic T lymphocytes reactive with vesicular stomatitis virus: analysis of specificity with monoclonal antibodies directed to the viral glycoprotein.
Authors: Lefrancois L , Lyles D S 
Published: December 2022

Abstract
A panel of monoclonal antibodies (MAb) reactive with the vesicular stomatitis virus (VSV) glycoprotein (G-protein) was used to inhibit lysis of infected target cells by cytotoxic T lymphocytes (CTL) reactive with VSV serotypes Indiana and New Jersey (VSV-Ind, VSV-NJ). MAb to distinct epitopes on the VSV-NJ G-protein were able to block lysis of VSV-NJ-infected targets using anti-VSV-NJ CTL. Furthermore, when a combination of MAb to three distinct epitopes was used, increased inhibition was observed when compared to single epitope blocking. Cross-reactive CTL generated using either VSV-NJ or VSV-Ind could be inhibited by MAb specific for the heterologous virus in blocking assays. Cross-reactive MAb also were able to block both serotype-specific and cross-reactive lysis. Antigenic variants selected with some of the MAb used in blocking studies were used to infect target cells. Reduction in lysis was not observed using variants with mutations at several epitopes. This result suggests that blocking by MAb involves steric hindrance of CTL-recognized determinants proximal to the MAb binding site.
Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions.
Authors: Natali P G , Cavaliere R , Bigotti A , Nicotra M R , Russo C , Ng A K , Giacomini P , Ferrone S 
Published: December 2022

Abstract
The antigenic heterogeneity of primary and metastatic lesions surgically removed from nine patients with nodular melanoma was investigated by using monoclonal antibodies to HLA-A, B antigens, to beta 2-microglobulin, to Ia antigens, and to melanoma-associated antigens (MAA). The latter include three types of membrane-bound MAA and a cytoplasmic MAA. In spite of an homogeneous morphologic appearance, multiple lesions removed from the same patient differed significantly in their reactivity with the panel of monoclonal antibodies in indirect immunofluorescence test. The extent of antigenic heterogeneity did not correlate with melanin synthesis, site of origin of the primary tumor, site of metastatic foci, or treatment, but was less marked in patients carrying the primary tumor. The antigenic heterogeneity of multiple lesions removed from one patient and the independent expression of the various types of MAA investigated suggest that combinations of monoclonal antibodies to MAA may be more effective than single antibodies for radioimaging and immunotherapy.
Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates.
Authors: Mew D , Wat C K , Towers G H , Levy J G 
Published: December 2022

Abstract
The term "photoimmunotherapy" describes an anti-cancer treatment that combines the phototoxic effects of chemical such as hematoporphyrin and the target-seeking ability of antibodies. Hematoporphyrin was chemically coupled to monoclonal antibodies directed to the DBA/2J myosarcoma M-1. Administration of anti-M-1-hematoporphyrin conjugates i.v. to M-1 tumor-bearing animals followed by exposure to incandescent light resulted in suppression of M-1 growth. The time interval between injection and light exposure was an important parameter in terms of tumor suppression. Tumor-bearing animals maintained in the dark for 96 to 196 hr after hematoporphyrin-antibody injection followed by 4-hr light exposure demonstrated significantly lower tumor incidence and longer latency periods, in comparison to conjugate-treated animals instantly exposed to light. The growth inhibiting properties of the conjugate appeared to be M-1-specific; it had no effect on the growth of a C57BL/6J lymphoma EL4. In addition, conjugates made with a nonspecific monoclonal antibody did not have any specific anti-tumor effect on M-1 growth. Treatment with equivalent doses of hematoporphyrin or antibody had no significant inhibiting effect on tumor growth. Clearly, the homing ability of the specific monoclonal antibody-hematoporphyrin conjugate was essential for effective drug delivery and inhibition of tumor growth.
Autoimmune effector cells. V.A monoclonal antibody specific for rat helper T lymphocytes inhibits adoptive transfer of autoimmune encephalomyelitis.
Authors: Swanborg R H 
Published: December 2022

Abstract
The in vitro activation of spleen cells from donor rats immunized with myelin basic protein results in enhanced adoptive transfer of experimental allergic encephalomyelitis to syngeneic recipients. In this study, adoptive transfer was inhibited when monoclonal antibody W3/25, which defines an antigen on rat helper T lymphocytes, was included in the in vitro cultures. Partial inhibition was achieved with monoclonal antibody OX-3, which recognizes la antigen, whereas other anti-T cell monoclonal reagents were ineffective. These results support the conclusion that W3/25+T cells play an essential role in the induction of this autoimmune response.
A requirement for helper T cells in the induction of delayed-type hypersensitivity.
Authors: Wright K , Ramshaw I A 
Published: December 2022

Abstract
This paper describes a model system for studying the role of helper T cells in the induction of delayed-type hypersensitivity (DTH). Cyclophosphamide- (CP) treated mice sensitized with antigen 3 days later develop high levels of delayed-type immunity; however, DTH cannot be demonstrated in mice that are sensitized with antigen 1 day after drug treatment. The inability to respond to antigen 1 day after CP treatment can be restored if either normal or low-dose primed spleen cells are transferred at the time of sensitization. Although irradiated (1500 rad) normal spleen cells are unable to restore DTH, such treatment has no effect on the primed spleen cell population. The lymphocytes responsible for restoring the DTH response were identified as T cells, in that treatment with anti-Thy-1.2 serum and C abrogated their effect. Furthermore, restoration of the DTH response was dependent on the presence of antigen at the time of lymphocyte transfer; irradiated primed cells could not transfer DTH alone. The DTH effector cells in reconstituted mice were identified as originating from the host and not from the transferred cell population. This was accomplished by using anti-H-2 serum to identify the source of the DTH effector cells after transferring parental (H-2b) irradiated primed spleen cells into CP-treated F1 mice (H-2b,k). Thus, the irradiated transferred cells are behaving as helper T cells and promoting the development of DTH effector cells in the host.